Nutrient chapter

Cucurbitacins

Context-specific entity; species, compartment and exposure are stated on each claim.

57 recorded mechanisms · 5 availability situations · 4 preserved sources. Draft and verified records are labeled separately.

Read recorded mechanisms Open recursive mind map

The mechanisms

What the sources say this nutrient does, one relationship at a time. Plain wording comes first; the technical statement follows.

Incubating purified human cofilin 1 with cucurbitacin D produced covalent adducts; mass shifts were compatible with about four compound molecules per cofilin under the tested excess-compound conditions.
Cucurbitacin D → Human cofilin 1 / CFL1 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text PMC3751690
experimental_model
Purified human cofilin 1, 5 micromolar; up to 1:100 protein:compound molar ratio, 16 hours.
limitations
Long, high-excess biochemical incubation; does not establish selectivity or occupancy after human ingestion.
nutrient_topic
Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Cucurbitacins
plain_language
Protein cysteines can become chemical attachment sites.
primary_references
Cucurbitacin covalent bonding to cysteine thiols: the filamentous-actin severing protein Cofilin1 as an exemplary target. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23945128/ · DOI 10.1186/1478-811X-11-58
Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 12–18
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified human cofilin 1, 5 micromolar; up to 1:100 protein:compound molar ratio, 16 hours. · source_derived_draft · unverified_draft
## cucurbitacin-d-cofilin-adduct Protein cysteines can become chemical attachment sites. Incubating purified human cofilin 1 with cucurbitacin D produced covalent adducts; mass shifts were compatible with about four compound molecules per cofilin under the tested excess-compound conditions. Model: Purified human cofilin 1, 5 micromolar; up to 1:100 protein:compound molar ratio, 16 hours. Limitations: Long, high-excess biochemical incubation; does not establish selectivity or occupancy after human ingestion. Evidence access: Primary full text PMC3751690 Cucurbitacin covalent bonding to cysteine thiols: the filamentous-actin severing protein Cofilin1 as an exemplary target. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23945128/ · DOI 10.1186/1478-811X-11-58
Complete structured claim and evidence
Incubating purified human cofilin 1 with cucurbitacin E produced covalent adducts; mass shifts were compatible with about four compound molecules per cofilin under the tested excess-compound conditions.
Cucurbitacin E → Human cofilin 1 / CFL1 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text PMC3751690
experimental_model
Purified human cofilin 1, 5 micromolar; up to 1:100 protein:compound molar ratio, 16 hours.
limitations
Long, high-excess biochemical incubation; does not establish selectivity or occupancy after human ingestion.
nutrient_topic
Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Cucurbitacins
plain_language
Protein cysteines can become chemical attachment sites.
primary_references
Cucurbitacin covalent bonding to cysteine thiols: the filamentous-actin severing protein Cofilin1 as an exemplary target. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23945128/ · DOI 10.1186/1478-811X-11-58
Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 20–26
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified human cofilin 1, 5 micromolar; up to 1:100 protein:compound molar ratio, 16 hours. · source_derived_draft · unverified_draft
## cucurbitacin-e-cofilin-adduct Protein cysteines can become chemical attachment sites. Incubating purified human cofilin 1 with cucurbitacin E produced covalent adducts; mass shifts were compatible with about four compound molecules per cofilin under the tested excess-compound conditions. Model: Purified human cofilin 1, 5 micromolar; up to 1:100 protein:compound molar ratio, 16 hours. Limitations: Long, high-excess biochemical incubation; does not establish selectivity or occupancy after human ingestion. Evidence access: Primary full text PMC3751690 Cucurbitacin covalent bonding to cysteine thiols: the filamentous-actin severing protein Cofilin1 as an exemplary target. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23945128/ · DOI 10.1186/1478-811X-11-58
Complete structured claim and evidence
Incubating purified human cofilin 1 with cucurbitacin I produced covalent adducts; mass shifts were compatible with about four compound molecules per cofilin under the tested excess-compound conditions.
Cucurbitacin I → Human cofilin 1 / CFL1 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text PMC3751690
experimental_model
Purified human cofilin 1, 5 micromolar; up to 1:100 protein:compound molar ratio, 16 hours.
limitations
Long, high-excess biochemical incubation; does not establish selectivity or occupancy after human ingestion.
nutrient_topic
Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Cucurbitacins
plain_language
Protein cysteines can become chemical attachment sites.
primary_references
Cucurbitacin covalent bonding to cysteine thiols: the filamentous-actin severing protein Cofilin1 as an exemplary target. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23945128/ · DOI 10.1186/1478-811X-11-58
Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 28–34
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified human cofilin 1, 5 micromolar; up to 1:100 protein:compound molar ratio, 16 hours. · source_derived_draft · unverified_draft
## cucurbitacin-i-cofilin-adduct Protein cysteines can become chemical attachment sites. Incubating purified human cofilin 1 with cucurbitacin I produced covalent adducts; mass shifts were compatible with about four compound molecules per cofilin under the tested excess-compound conditions. Model: Purified human cofilin 1, 5 micromolar; up to 1:100 protein:compound molar ratio, 16 hours. Limitations: Long, high-excess biochemical incubation; does not establish selectivity or occupancy after human ingestion. Evidence access: Primary full text PMC3751690 Cucurbitacin covalent bonding to cysteine thiols: the filamentous-actin severing protein Cofilin1 as an exemplary target. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23945128/ · DOI 10.1186/1478-811X-11-58
Complete structured claim and evidence
Mass spectrometry localized cucurbitacin E modification to cofilin Cys39, Cys80 and Cys139, with weaker evidence for Cys147.
Cucurbitacin E → Human cofilin 1 / CFL1 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text PMC3751690
experimental_model
Purified human cofilin 1 biochemical mapping.
limitations
A protein cysteine residue is not equivalent to free dietary cysteine; these data do not quantify nutritional depletion.
nutrient_topic
Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Cucurbitacins
plain_language
The study identifies individual protein attachment sites.
primary_references
Cucurbitacin covalent bonding to cysteine thiols: the filamentous-actin severing protein Cofilin1 as an exemplary target. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23945128/ · DOI 10.1186/1478-811X-11-58
Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 36–42
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified human cofilin 1 biochemical mapping. · source_derived_draft · unverified_draft
## cucurbitacin-e-cofilin-sites The study identifies individual protein attachment sites. Mass spectrometry localized cucurbitacin E modification to cofilin Cys39, Cys80 and Cys139, with weaker evidence for Cys147. Model: Purified human cofilin 1 biochemical mapping. Limitations: A protein cysteine residue is not equivalent to free dietary cysteine; these data do not quantify nutritional depletion. Evidence access: Primary full text PMC3751690 Cucurbitacin covalent bonding to cysteine thiols: the filamentous-actin severing protein Cofilin1 as an exemplary target. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23945128/ · DOI 10.1186/1478-811X-11-58
Complete structured claim and evidence
Cucurbitacin E pretreatment inhibited the F-actin-severing activity of purified human cofilin 1.
Cucurbitacin E → Human cofilin-mediated F-actin severing source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text PMC3751690
experimental_model
Purified-protein functional assay.
limitations
Actin preparation species is not resolved in this record; broad thiol reactivity prevents assigning cofilin as the exclusive cellular target.
nutrient_topic
Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Cucurbitacins
plain_language
Modifying the cutting protein slows filament disassembly.
primary_references
Cucurbitacin covalent bonding to cysteine thiols: the filamentous-actin severing protein Cofilin1 as an exemplary target. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23945128/ · DOI 10.1186/1478-811X-11-58
Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 44–50
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified-protein functional assay. · source_derived_draft · unverified_draft
## cucurbitacin-e-cofilin-severing Modifying the cutting protein slows filament disassembly. Cucurbitacin E pretreatment inhibited the F-actin-severing activity of purified human cofilin 1. Model: Purified-protein functional assay. Limitations: Actin preparation species is not resolved in this record; broad thiol reactivity prevents assigning cofilin as the exclusive cellular target. Evidence access: Primary full text PMC3751690 Cucurbitacin covalent bonding to cysteine thiols: the filamentous-actin severing protein Cofilin1 as an exemplary target. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23945128/ · DOI 10.1186/1478-811X-11-58
Complete structured claim and evidence
Cucurbitacin E covalently modified actin at Cys257 in F-actin and inhibited depolymerization, with effects at substoichiometric compound:actin ratios down to 1:6.
Cucurbitacin E → Purified F-actin in cucurbitacin assays, species as reported source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Purified actin and cellular photoactivation experiments.
limitations
Purified actin species/isoform not established from the accessed abstract; not automatically human ACTB. This study did not find an effect on polymerization.
nutrient_topic
Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Cucurbitacins
plain_language
The filament itself can be stabilized.
primary_references
The natural product cucurbitacin E inhibits depolymerization of actin filaments. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22724897/ · DOI 10.1021/cb300254s
Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 52–58
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified actin and cellular photoactivation experiments. · source_derived_draft · unverified_draft
## cucurbitacin-e-f-actin The filament itself can be stabilized. Cucurbitacin E covalently modified actin at Cys257 in F-actin and inhibited depolymerization, with effects at substoichiometric compound:actin ratios down to 1:6. Model: Purified actin and cellular photoactivation experiments. Limitations: Purified actin species/isoform not established from the accessed abstract; not automatically human ACTB. This study did not find an effect on polymerization. Evidence access: Primary abstract The natural product cucurbitacin E inhibits depolymerization of actin filaments. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22724897/ · DOI 10.1021/cb300254s
Complete structured claim and evidence
The cucurbitacin E actin study reported binding to filamentous actin but not globular actin.
Cucurbitacin E → Purified G-actin in cucurbitacin assays, species as reported source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Same purified-actin experiments.
limitations
Member-specific assay result; cannot be transferred to cucurbitacin I.
nutrient_topic
Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Cucurbitacins
plain_language
The physical state of the protein changes the result.
primary_references
The natural product cucurbitacin E inhibits depolymerization of actin filaments. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22724897/ · DOI 10.1021/cb300254s
Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 60–66
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Same purified-actin experiments. · source_derived_draft · unverified_draft
## cucurbitacin-e-no-g-actin-binding The physical state of the protein changes the result. The cucurbitacin E actin study reported binding to filamentous actin but not globular actin. Model: Same purified-actin experiments. Limitations: Member-specific assay result; cannot be transferred to cucurbitacin I. Evidence access: Primary abstract The natural product cucurbitacin E inhibits depolymerization of actin filaments. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22724897/ · DOI 10.1021/cb300254s
Complete structured claim and evidence
Adding cucurbitacin I rapidly reduced motility and produced actin aggregates in canine MDCK cells.
Cucurbitacin I → Canine MDCK cell motility during cucurbitacin I exposure source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text PMC2991314
experimental_model
Canine MDCK cellular experiments; also mouse B16-F1 experiments in the paper.
limitations
Cellular phenotype does not identify a direct molecular binding target.
nutrient_topic
Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Cucurbitacins
plain_language
Cell movement changes along with filament organization.
primary_references
Cucurbitacin I inhibits cell motility by indirectly interfering with actin dynamics. · 2010 · https://pubmed.ncbi.nlm.nih.gov/21124831/ · DOI 10.1371/journal.pone.0014039
Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 68–74
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Canine MDCK cellular experiments; also mouse B16-F1 experiments in the paper. · source_derived_draft · unverified_draft
## cucurbitacin-i-canine-motility Cell movement changes along with filament organization. Adding cucurbitacin I rapidly reduced motility and produced actin aggregates in canine MDCK cells. Model: Canine MDCK cellular experiments; also mouse B16-F1 experiments in the paper. Limitations: Cellular phenotype does not identify a direct molecular binding target. Evidence access: Primary full text PMC2991314 Cucurbitacin I inhibits cell motility by indirectly interfering with actin dynamics. · 2010 · https://pubmed.ncbi.nlm.nih.gov/21124831/ · DOI 10.1371/journal.pone.0014039
Complete structured claim and evidence
In the 2010 purified-actin assays, cucurbitacin I did not change depolymerization rate at concentrations active in cells; high concentrations delayed polymerization initiation without changing its subsequent rate.
Cucurbitacin I → Purified F-actin in cucurbitacin assays, species as reported source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text PMC2991314
experimental_model
Purified-actin experiments alongside canine and mouse cell models.
limitations
Different member, concentration and endpoint from cucurbitacin E stabilization; not an automatic scientific contradiction.
nutrient_topic
Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Cucurbitacins
plain_language
A dramatic cell phenotype was not reproduced by every purified-actin endpoint.
primary_references
Cucurbitacin I inhibits cell motility by indirectly interfering with actin dynamics. · 2010 · https://pubmed.ncbi.nlm.nih.gov/21124831/ · DOI 10.1371/journal.pone.0014039
Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 76–82
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified-actin experiments alongside canine and mouse cell models. · source_derived_draft · unverified_draft
## cucurbitacin-i-no-depolymerization-effect A dramatic cell phenotype was not reproduced by every purified-actin endpoint. In the 2010 purified-actin assays, cucurbitacin I did not change depolymerization rate at concentrations active in cells; high concentrations delayed polymerization initiation without changing its subsequent rate. Model: Purified-actin experiments alongside canine and mouse cell models. Limitations: Different member, concentration and endpoint from cucurbitacin E stabilization; not an automatic scientific contradiction. Evidence access: Primary full text PMC2991314 Cucurbitacin I inhibits cell motility by indirectly interfering with actin dynamics. · 2010 · https://pubmed.ncbi.nlm.nih.gov/21124831/ · DOI 10.1371/journal.pone.0014039
Complete structured claim and evidence
Cucurbitacin I at 1–200 nM increased G-actin thermal stability in a thermal-shift assay, supporting an interaction in that preparation.
Cucurbitacin I → Purified G-actin in cucurbitacin assays, species as reported source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
2024 G-actin thermal-shift experiment; protein species not established by the accessed abstract.
limitations
A thermal shift is not an affinity measurement, covalent-site map or proof of selectivity.
nutrient_topic
Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Cucurbitacins
plain_language
A later experiment found evidence of interaction with actin monomers.
primary_references
Depolymerization of actin filaments by Cucurbitacin I through binding G-actin. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38370084/ · DOI 10.1002/fsn3.3804
Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 84–90
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · 2024 G-actin thermal-shift experiment; protein species not established by the accessed abstract. · source_derived_draft · unverified_draft
## cucurbitacin-i-g-actin-shift A later experiment found evidence of interaction with actin monomers. Cucurbitacin I at 1–200 nM increased G-actin thermal stability in a thermal-shift assay, supporting an interaction in that preparation. Model: 2024 G-actin thermal-shift experiment; protein species not established by the accessed abstract. Limitations: A thermal shift is not an affinity measurement, covalent-site map or proof of selectivity. Evidence access: Primary abstract Depolymerization of actin filaments by Cucurbitacin I through binding G-actin. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38370084/ · DOI 10.1002/fsn3.3804
Complete structured claim and evidence
Adding cucurbitacin I inhibited actin polymerization in the 2024 in-vitro experiment.
Cucurbitacin I → Purified actin polymerization in the 2024 cucurbitacin I assay source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Purified actin plus endothelial-cell experiments; cell species not resolved in this abstract-based record.
limitations
Concentration-dependent and assay-dependent findings require matched replication before declaring a resolved direct-target disagreement.
nutrient_topic
Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Cucurbitacins
plain_language
Filament assembly is a separate endpoint from filament breakdown.
primary_references
Depolymerization of actin filaments by Cucurbitacin I through binding G-actin. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38370084/ · DOI 10.1002/fsn3.3804
Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 92–98
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified actin plus endothelial-cell experiments; cell species not resolved in this abstract-based record. · source_derived_draft · unverified_draft
## cucurbitacin-i-polymerization Filament assembly is a separate endpoint from filament breakdown. Adding cucurbitacin I inhibited actin polymerization in the 2024 in-vitro experiment. Model: Purified actin plus endothelial-cell experiments; cell species not resolved in this abstract-based record. Limitations: Concentration-dependent and assay-dependent findings require matched replication before declaring a resolved direct-target disagreement. Evidence access: Primary abstract Depolymerization of actin filaments by Cucurbitacin I through binding G-actin. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38370084/ · DOI 10.1002/fsn3.3804
Complete structured claim and evidence
Docking and molecular dynamics proposed cucurbitacin I contacts involving actin residues I136, I175, D154 and A138.
Cucurbitacin I → Purified G-actin in cucurbitacin assays, species as reported source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Computational structural modeling in the 2024 actin paper.
limitations
No ligand-bound experimental structure or covalent mapping was established by this computation.
nutrient_topic
Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Cucurbitacins
plain_language
The proposed contact map is a prediction.
primary_references
Depolymerization of actin filaments by Cucurbitacin I through binding G-actin. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38370084/ · DOI 10.1002/fsn3.3804
Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 100–106
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Computational structural modeling in the 2024 actin paper. · source_derived_draft · unverified_draft
## cucurbitacin-i-docking The proposed contact map is a prediction. Docking and molecular dynamics proposed cucurbitacin I contacts involving actin residues I136, I175, D154 and A138. Model: Computational structural modeling in the 2024 actin paper. Limitations: No ligand-bound experimental structure or covalent mapping was established by this computation. Evidence access: Primary abstract Depolymerization of actin filaments by Cucurbitacin I through binding G-actin. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38370084/ · DOI 10.1002/fsn3.3804
Complete structured claim and evidence
UV spectroscopy and FTICR mass spectrometry detected physical interaction between cucurbitacin B and glutathione in a cell-free system.
Cucurbitacin B → GSH source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Cell-free chemistry; exposure concentration and duration unavailable in the accessed abstract.
limitations
Physical interaction is not a quantified in-vivo detoxification rate or human glutathione-depletion threshold.
nutrient_topic
Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Cucurbitacins
plain_language
Glutathione can interact with the compound before a downstream signal is measured.
primary_references
Cucurbitacin B potently suppresses non-small-cell lung cancer growth: identification of intracellular thiols as critical targets. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23340170/ · DOI 10.1016/j.canlet.2013.01.008
Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 108–114
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cell-free chemistry; exposure concentration and duration unavailable in the accessed abstract. · source_derived_draft · unverified_draft
## cucurbitacin-b-gsh-interaction Glutathione can interact with the compound before a downstream signal is measured. UV spectroscopy and FTICR mass spectrometry detected physical interaction between cucurbitacin B and glutathione in a cell-free system. Model: Cell-free chemistry; exposure concentration and duration unavailable in the accessed abstract. Limitations: Physical interaction is not a quantified in-vivo detoxification rate or human glutathione-depletion threshold. Evidence access: Primary abstract Cucurbitacin B potently suppresses non-small-cell lung cancer growth: identification of intracellular thiols as critical targets. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23340170/ · DOI 10.1016/j.canlet.2013.01.008
Complete structured claim and evidence
UV spectroscopy and FTICR mass spectrometry detected physical interaction between cucurbitacin B and N-acetylcysteine in a cell-free system.
Cucurbitacin B → N-Acetyl-L-cysteine source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Cell-free chemistry.
limitations
NAC rescue therefore does not uniquely prove ROS scavenging; it also does not rule out a role for ROS.
nutrient_topic
Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Cucurbitacins
plain_language
An antioxidant can also change the amount of available test compound.
primary_references
Cucurbitacin B potently suppresses non-small-cell lung cancer growth: identification of intracellular thiols as critical targets. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23340170/ · DOI 10.1016/j.canlet.2013.01.008
Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 116–122
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cell-free chemistry. · source_derived_draft · unverified_draft
## cucurbitacin-b-nac-interaction An antioxidant can also change the amount of available test compound. UV spectroscopy and FTICR mass spectrometry detected physical interaction between cucurbitacin B and N-acetylcysteine in a cell-free system. Model: Cell-free chemistry. Limitations: NAC rescue therefore does not uniquely prove ROS scavenging; it also does not rule out a role for ROS. Evidence access: Primary abstract Cucurbitacin B potently suppresses non-small-cell lung cancer growth: identification of intracellular thiols as critical targets. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23340170/ · DOI 10.1016/j.canlet.2013.01.008
Complete structured claim and evidence
Adding cucurbitacin B rapidly lowered measured protein-thiol levels in human NSCLC cells.
Cucurbitacin B → Human NSCLC cellular protein-thiol pool source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human H1299, A549, HCC827 and H661 study panel; exact assay allocation and dose not resolved from the abstract.
limitations
A cellular thiol measurement is not evidence of whole-body cysteine deficiency.
nutrient_topic
Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Cucurbitacins
plain_language
Reactive protein groups decreased after exposure.
primary_references
Cucurbitacin B potently suppresses non-small-cell lung cancer growth: identification of intracellular thiols as critical targets. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23340170/ · DOI 10.1016/j.canlet.2013.01.008
Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 124–130
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human H1299, A549, HCC827 and H661 study panel; exact assay allocation and dose not resolved from the abstract. · source_derived_draft · unverified_draft
## cucurbitacin-b-thiol-loss Reactive protein groups decreased after exposure. Adding cucurbitacin B rapidly lowered measured protein-thiol levels in human NSCLC cells. Model: Human H1299, A549, HCC827 and H661 study panel; exact assay allocation and dose not resolved from the abstract. Limitations: A cellular thiol measurement is not evidence of whole-body cysteine deficiency. Evidence access: Primary abstract Cucurbitacin B potently suppresses non-small-cell lung cancer growth: identification of intracellular thiols as critical targets. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23340170/ · DOI 10.1016/j.canlet.2013.01.008
Complete structured claim and evidence
Cucurbitacin B exposure lowered the GSH/GSSG ratio in the human NSCLC experiments.
Cucurbitacin B → Human NSCLC GSH/GSSG ratio during cucurbitacin B exposure source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human NSCLC cell study.
limitations
A ratio alone does not establish which synthesis, oxidation, conjugation or export flux caused the change.
nutrient_topic
Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Cucurbitacins
plain_language
The redox balance shifted alongside toxicity.
primary_references
Cucurbitacin B potently suppresses non-small-cell lung cancer growth: identification of intracellular thiols as critical targets. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23340170/ · DOI 10.1016/j.canlet.2013.01.008
Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 132–138
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human NSCLC cell study. · source_derived_draft · unverified_draft
## cucurbitacin-b-redox-ratio The redox balance shifted alongside toxicity. Cucurbitacin B exposure lowered the GSH/GSSG ratio in the human NSCLC experiments. Model: Human NSCLC cell study. Limitations: A ratio alone does not establish which synthesis, oxidation, conjugation or export flux caused the change. Evidence access: Primary abstract Cucurbitacin B potently suppresses non-small-cell lung cancer growth: identification of intracellular thiols as critical targets. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23340170/ · DOI 10.1016/j.canlet.2013.01.008
Complete structured claim and evidence
Pretreating human NSCLC cells with the glutathione-synthesis inhibitor BSO increased cucurbitacin B cytotoxicity.
L-Buthionine-S-sulfoximine / BSO → Human NSCLC cytotoxic response to cucurbitacin B source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Pharmacological inhibition in human cancer-cell experiments; dose/duration not in accessed abstract.
limitations
Experimental synthesis inhibition is not a dietary cucurbitacin deficiency or evidence that oral glutathione protects people.
nutrient_topic
Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Cucurbitacins
plain_language
Weakening glutathione production increased sensitivity in this model.
primary_references
Cucurbitacin B potently suppresses non-small-cell lung cancer growth: identification of intracellular thiols as critical targets. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23340170/ · DOI 10.1016/j.canlet.2013.01.008
trigger_kind
machinery_impairment Imported condition classification; unverified.
Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 140–146
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Pharmacological inhibition in human cancer-cell experiments; dose/duration not in accessed abstract. · source_derived_draft · unverified_draft
## cucurbitacin-b-bso-sensitivity Weakening glutathione production increased sensitivity in this model. Pretreating human NSCLC cells with the glutathione-synthesis inhibitor BSO increased cucurbitacin B cytotoxicity. Model: Pharmacological inhibition in human cancer-cell experiments; dose/duration not in accessed abstract. Limitations: Experimental synthesis inhibition is not a dietary cucurbitacin deficiency or evidence that oral glutathione protects people. Evidence access: Primary abstract Cucurbitacin B potently suppresses non-small-cell lung cancer growth: identification of intracellular thiols as critical targets. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23340170/ · DOI 10.1016/j.canlet.2013.01.008
Complete structured claim and evidence
Adding N-acetylcysteine attenuated the reported cucurbitacin B cellular effects in the human NSCLC study.
N-Acetyl-L-cysteine → Human NSCLC cytotoxic response to cucurbitacin B source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human NSCLC experiments plus separate cell-free interaction assays.
limitations
Compound trapping and redox effects are not distinguished by rescue alone.
nutrient_topic
Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Cucurbitacins
plain_language
Thiol availability changed the experimental response.
primary_references
Cucurbitacin B potently suppresses non-small-cell lung cancer growth: identification of intracellular thiols as critical targets. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23340170/ · DOI 10.1016/j.canlet.2013.01.008
Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 148–154
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human NSCLC experiments plus separate cell-free interaction assays. · source_derived_draft · unverified_draft
## cucurbitacin-b-nac-rescue Thiol availability changed the experimental response. Adding N-acetylcysteine attenuated the reported cucurbitacin B cellular effects in the human NSCLC study. Model: Human NSCLC experiments plus separate cell-free interaction assays. Limitations: Compound trapping and redox effects are not distinguished by rescue alone. Evidence access: Primary abstract Cucurbitacin B potently suppresses non-small-cell lung cancer growth: identification of intracellular thiols as critical targets. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23340170/ · DOI 10.1016/j.canlet.2013.01.008
Complete structured claim and evidence
Cucurbitacin I reduced heregulin-evoked Rac1 activation in human breast-cancer cells.
Cucurbitacin I → RAC1 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human breast-cancer cell experiments; representative 0.1 micromolar exposure for 1 hour.
limitations
Activity change is not direct Rac1 binding.
nutrient_topic
Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Cucurbitacins
plain_language
A movement-control switch became less active.
primary_references
Cucurbitacin I inhibits Rac1 activation in breast cancer cells by a reactive oxygen species-mediated mechanism and independently of Janus tyrosine kinase 2 and P-Rex1. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23478800/ · DOI 10.1124/mol.112.084293
Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 156–162
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human breast-cancer cell experiments; representative 0.1 micromolar exposure for 1 hour. · source_derived_draft · unverified_draft
## cucurbitacin-i-rac1 A movement-control switch became less active. Cucurbitacin I reduced heregulin-evoked Rac1 activation in human breast-cancer cells. Model: Human breast-cancer cell experiments; representative 0.1 micromolar exposure for 1 hour. Limitations: Activity change is not direct Rac1 binding. Evidence access: Primary abstract Cucurbitacin I inhibits Rac1 activation in breast cancer cells by a reactive oxygen species-mediated mechanism and independently of Janus tyrosine kinase 2 and P-Rex1. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23478800/ · DOI 10.1124/mol.112.084293
Complete structured claim and evidence
Cucurbitacin I activated RhoA/ROCK signaling; disrupting this pathway prevented the observed Rac1 inhibition.
Cucurbitacin I → Human RhoA / RHOA source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human breast-cancer cellular perturbation experiments.
limitations
ROCK isoform is not resolved in this record; pathway dependence does not establish a direct cucurbitacin target.
nutrient_topic
Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Cucurbitacins
plain_language
One cytoskeletal pathway helped suppress another.
primary_references
Cucurbitacin I inhibits Rac1 activation in breast cancer cells by a reactive oxygen species-mediated mechanism and independently of Janus tyrosine kinase 2 and P-Rex1. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23478800/ · DOI 10.1124/mol.112.084293
Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 164–170
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human breast-cancer cellular perturbation experiments. · source_derived_draft · unverified_draft
## cucurbitacin-i-rhoa-rock One cytoskeletal pathway helped suppress another. Cucurbitacin I activated RhoA/ROCK signaling; disrupting this pathway prevented the observed Rac1 inhibition. Model: Human breast-cancer cellular perturbation experiments. Limitations: ROCK isoform is not resolved in this record; pathway dependence does not establish a direct cucurbitacin target. Evidence access: Primary abstract Cucurbitacin I inhibits Rac1 activation in breast cancer cells by a reactive oxygen species-mediated mechanism and independently of Janus tyrosine kinase 2 and P-Rex1. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23478800/ · DOI 10.1124/mol.112.084293
Complete structured claim and evidence
Silencing STAT3 or JAK2 did not reproduce cucurbitacin I-mediated Rac1 inhibition in the tested human breast-cancer cells.
STAT3 → RAC1 source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
RNA interference in human breast-cancer cells.
limitations
Negative pathway test is limited to these endpoints and cells; it does not show that all JAK/STAT effects are absent.
nutrient_topic
Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Cucurbitacins
plain_language
Removing the familiar signaling pathway did not explain this movement effect.
primary_references
Cucurbitacin I inhibits Rac1 activation in breast cancer cells by a reactive oxygen species-mediated mechanism and independently of Janus tyrosine kinase 2 and P-Rex1. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23478800/ · DOI 10.1124/mol.112.084293
trigger_kind
machinery_impairment Imported condition classification; unverified.
Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 172–178
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · RNA interference in human breast-cancer cells. · source_derived_draft · unverified_draft
## cucurbitacin-i-jak-stat-knockdown Removing the familiar signaling pathway did not explain this movement effect. Silencing STAT3 or JAK2 did not reproduce cucurbitacin I-mediated Rac1 inhibition in the tested human breast-cancer cells. Model: RNA interference in human breast-cancer cells. Limitations: Negative pathway test is limited to these endpoints and cells; it does not show that all JAK/STAT effects are absent. Evidence access: Primary abstract Cucurbitacin I inhibits Rac1 activation in breast cancer cells by a reactive oxygen species-mediated mechanism and independently of Janus tyrosine kinase 2 and P-Rex1. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23478800/ · DOI 10.1124/mol.112.084293
Complete structured claim and evidence
Mito-TEMPO and NAC prevented tested cucurbitacin I effects on Rac1 activation, supporting mitochondrial ROS involvement alongside the thiol-interception caveat for NAC.
Mito-TEMPO → RAC1 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human breast-cancer pharmacology.
limitations
Probe rescue does not identify the ROS-generating enzyme or prove the same route after human ingestion.
nutrient_topic
Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Cucurbitacins
plain_language
Two different probes help test the oxidative-stress route.
primary_references
Cucurbitacin I inhibits Rac1 activation in breast cancer cells by a reactive oxygen species-mediated mechanism and independently of Janus tyrosine kinase 2 and P-Rex1. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23478800/ · DOI 10.1124/mol.112.084293
Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 180–186
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human breast-cancer pharmacology. · source_derived_draft · unverified_draft
## cucurbitacin-i-mitoros-rescue Two different probes help test the oxidative-stress route. Mito-TEMPO and NAC prevented tested cucurbitacin I effects on Rac1 activation, supporting mitochondrial ROS involvement alongside the thiol-interception caveat for NAC. Model: Human breast-cancer pharmacology. Limitations: Probe rescue does not identify the ROS-generating enzyme or prove the same route after human ingestion. Evidence access: Primary abstract Cucurbitacin I inhibits Rac1 activation in breast cancer cells by a reactive oxygen species-mediated mechanism and independently of Janus tyrosine kinase 2 and P-Rex1. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23478800/ · DOI 10.1124/mol.112.084293
Complete structured claim and evidence
Cucurbitacin B lowered TNF receptor 1 expression in human A549 cells without reducing the measured TRADD, RIPK1 and TRAF2 adaptor proteins.
Cucurbitacin B → Human TNF receptor 1 / TNFRSF1A source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
TNF-alpha-stimulated human A549 cells; dose/time not resolved in accessed abstract.
limitations
Protein abundance result, not demonstrated direct binding to TNFR1.
nutrient_topic
Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Cucurbitacins
plain_language
The receptor changed before treating all downstream proteins as depleted.
primary_references
Cucurbitacin B Down-Regulates TNF Receptor 1 Expression and Inhibits the TNF-α-Dependent Nuclear Factor κB Signaling Pathway in Human Lung Adenocarcinoma A549 Cells. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35806134/ · DOI 10.3390/ijms23137130
Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 188–194
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · TNF-alpha-stimulated human A549 cells; dose/time not resolved in accessed abstract. · source_derived_draft · unverified_draft
## cucurbitacin-b-tnfr1 The receptor changed before treating all downstream proteins as depleted. Cucurbitacin B lowered TNF receptor 1 expression in human A549 cells without reducing the measured TRADD, RIPK1 and TRAF2 adaptor proteins. Model: TNF-alpha-stimulated human A549 cells; dose/time not resolved in accessed abstract. Limitations: Protein abundance result, not demonstrated direct binding to TNFR1. Evidence access: Primary abstract Cucurbitacin B Down-Regulates TNF Receptor 1 Expression and Inhibits the TNF-α-Dependent Nuclear Factor κB Signaling Pathway in Human Lung Adenocarcinoma A549 Cells. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35806134/ · DOI 10.3390/ijms23137130
Complete structured claim and evidence
Adding a TNF-alpha-converting-enzyme inhibitor suppressed cucurbitacin B-associated TNFR1 down-regulation in human A549 cells.
Human ADAM metallopeptidase domain 17 / ADAM17 → Human TNF receptor 1 / TNFRSF1A source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Human A549 pharmacological perturbation.
limitations
Supports involvement of ADAM17-related processing; does not prove cucurbitacin binds or directly activates ADAM17.
nutrient_topic
Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Cucurbitacins
plain_language
A receptor-processing enzyme was implicated by an inhibitor experiment.
primary_references
Cucurbitacin B Down-Regulates TNF Receptor 1 Expression and Inhibits the TNF-α-Dependent Nuclear Factor κB Signaling Pathway in Human Lung Adenocarcinoma A549 Cells. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35806134/ · DOI 10.3390/ijms23137130
trigger_kind
machinery_impairment Imported condition classification; unverified.
Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 196–202
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human A549 pharmacological perturbation. · source_derived_draft · unverified_draft
## cucurbitacin-b-adam17-gate A receptor-processing enzyme was implicated by an inhibitor experiment. Adding a TNF-alpha-converting-enzyme inhibitor suppressed cucurbitacin B-associated TNFR1 down-regulation in human A549 cells. Model: Human A549 pharmacological perturbation. Limitations: Supports involvement of ADAM17-related processing; does not prove cucurbitacin binds or directly activates ADAM17. Evidence access: Primary abstract Cucurbitacin B Down-Regulates TNF Receptor 1 Expression and Inhibits the TNF-α-Dependent Nuclear Factor κB Signaling Pathway in Human Lung Adenocarcinoma A549 Cells. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35806134/ · DOI 10.3390/ijms23137130
Complete structured claim and evidence
Cucurbitacin B reduced TNF-alpha-induced RelA nuclear translocation and I-kappa-B-alpha phosphorylation in human A549 cells.
Cucurbitacin B → Human NF-kappa-B subunit RelA / RELA source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human A549 cytokine-stimulation assays.
limitations
Downstream readouts do not establish direct inhibition of each protein.
nutrient_topic
Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Cucurbitacins
plain_language
Less inflammatory transcription signaling reached the nucleus.
primary_references
Cucurbitacin B Down-Regulates TNF Receptor 1 Expression and Inhibits the TNF-α-Dependent Nuclear Factor κB Signaling Pathway in Human Lung Adenocarcinoma A549 Cells. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35806134/ · DOI 10.3390/ijms23137130
Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 204–210
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human A549 cytokine-stimulation assays. · source_derived_draft · unverified_draft
## cucurbitacin-b-rela Less inflammatory transcription signaling reached the nucleus. Cucurbitacin B reduced TNF-alpha-induced RelA nuclear translocation and I-kappa-B-alpha phosphorylation in human A549 cells. Model: Human A549 cytokine-stimulation assays. Limitations: Downstream readouts do not establish direct inhibition of each protein. Evidence access: Primary abstract Cucurbitacin B Down-Regulates TNF Receptor 1 Expression and Inhibits the TNF-α-Dependent Nuclear Factor κB Signaling Pathway in Human Lung Adenocarcinoma A549 Cells. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35806134/ · DOI 10.3390/ijms23137130
Complete structured claim and evidence
Cucurbitacin B decreased ICAM1 expression induced by TNF-alpha or IL-1-alpha in human A549 cells.
Cucurbitacin B → Human intercellular adhesion molecule 1 / ICAM1 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human lung adenocarcinoma cell model.
limitations
This is not a clinical anti-inflammatory outcome.
nutrient_topic
Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Cucurbitacins
plain_language
A cell-adhesion response to inflammatory signals decreased.
primary_references
Cucurbitacin B Down-Regulates TNF Receptor 1 Expression and Inhibits the TNF-α-Dependent Nuclear Factor κB Signaling Pathway in Human Lung Adenocarcinoma A549 Cells. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35806134/ · DOI 10.3390/ijms23137130
Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 212–218
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human lung adenocarcinoma cell model. · source_derived_draft · unverified_draft
## cucurbitacin-b-icam A cell-adhesion response to inflammatory signals decreased. Cucurbitacin B decreased ICAM1 expression induced by TNF-alpha or IL-1-alpha in human A549 cells. Model: Human lung adenocarcinoma cell model. Limitations: This is not a clinical anti-inflammatory outcome. Evidence access: Primary abstract Cucurbitacin B Down-Regulates TNF Receptor 1 Expression and Inhibits the TNF-α-Dependent Nuclear Factor κB Signaling Pathway in Human Lung Adenocarcinoma A549 Cells. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35806134/ · DOI 10.3390/ijms23137130
Complete structured claim and evidence
Adding glutathione attenuated cucurbitacin B inhibition of TNF-alpha-induced ICAM1 expression; L-cysteine had a smaller effect than the other tested thiols.
GSH → Human intercellular adhesion molecule 1 / ICAM1 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human A549 cytokine-stimulation experiment.
limitations
The experiment supports a chemical-reactivity dependency; it does not establish a human supplement interaction magnitude.
nutrient_topic
Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Cucurbitacins
plain_language
A separately stored thiol changed the signaling result.
primary_references
Cucurbitacin B Down-Regulates TNF Receptor 1 Expression and Inhibits the TNF-α-Dependent Nuclear Factor κB Signaling Pathway in Human Lung Adenocarcinoma A549 Cells. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35806134/ · DOI 10.3390/ijms23137130
Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 220–226
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human A549 cytokine-stimulation experiment. · source_derived_draft · unverified_draft
## cucurbitacin-b-gsh-icam-rescue A separately stored thiol changed the signaling result. Adding glutathione attenuated cucurbitacin B inhibition of TNF-alpha-induced ICAM1 expression; L-cysteine had a smaller effect than the other tested thiols. Model: Human A549 cytokine-stimulation experiment. Limitations: The experiment supports a chemical-reactivity dependency; it does not establish a human supplement interaction magnitude. Evidence access: Primary abstract Cucurbitacin B Down-Regulates TNF Receptor 1 Expression and Inhibits the TNF-α-Dependent Nuclear Factor κB Signaling Pathway in Human Lung Adenocarcinoma A549 Cells. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35806134/ · DOI 10.3390/ijms23137130
Complete structured claim and evidence
Adding N-acetylcysteine attenuated cucurbitacin B inhibition of TNF-alpha-induced ICAM1 expression; L-cysteine had a smaller effect than the other tested thiols.
N-Acetyl-L-cysteine → Human intercellular adhesion molecule 1 / ICAM1 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human A549 cytokine-stimulation experiment.
limitations
The experiment supports a chemical-reactivity dependency; it does not establish a human supplement interaction magnitude.
nutrient_topic
Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Cucurbitacins
plain_language
A separately stored thiol changed the signaling result.
primary_references
Cucurbitacin B Down-Regulates TNF Receptor 1 Expression and Inhibits the TNF-α-Dependent Nuclear Factor κB Signaling Pathway in Human Lung Adenocarcinoma A549 Cells. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35806134/ · DOI 10.3390/ijms23137130
Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 228–234
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human A549 cytokine-stimulation experiment. · source_derived_draft · unverified_draft
## cucurbitacin-b-nac-icam-rescue A separately stored thiol changed the signaling result. Adding N-acetylcysteine attenuated cucurbitacin B inhibition of TNF-alpha-induced ICAM1 expression; L-cysteine had a smaller effect than the other tested thiols. Model: Human A549 cytokine-stimulation experiment. Limitations: The experiment supports a chemical-reactivity dependency; it does not establish a human supplement interaction magnitude. Evidence access: Primary abstract Cucurbitacin B Down-Regulates TNF Receptor 1 Expression and Inhibits the TNF-α-Dependent Nuclear Factor κB Signaling Pathway in Human Lung Adenocarcinoma A549 Cells. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35806134/ · DOI 10.3390/ijms23137130
Complete structured claim and evidence
Adding L-cysteine attenuated cucurbitacin B inhibition of TNF-alpha-induced ICAM1 expression; L-cysteine had a smaller effect than the other tested thiols.
L-Cysteine → Human intercellular adhesion molecule 1 / ICAM1 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human A549 cytokine-stimulation experiment.
limitations
The experiment supports a chemical-reactivity dependency; it does not establish a human supplement interaction magnitude.
nutrient_topic
Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Cucurbitacins
plain_language
A separately stored thiol changed the signaling result.
primary_references
Cucurbitacin B Down-Regulates TNF Receptor 1 Expression and Inhibits the TNF-α-Dependent Nuclear Factor κB Signaling Pathway in Human Lung Adenocarcinoma A549 Cells. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35806134/ · DOI 10.3390/ijms23137130
Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 236–242
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human A549 cytokine-stimulation experiment. · source_derived_draft · unverified_draft
## cucurbitacin-b-cysteine-icam-rescue A separately stored thiol changed the signaling result. Adding L-cysteine attenuated cucurbitacin B inhibition of TNF-alpha-induced ICAM1 expression; L-cysteine had a smaller effect than the other tested thiols. Model: Human A549 cytokine-stimulation experiment. Limitations: The experiment supports a chemical-reactivity dependency; it does not establish a human supplement interaction magnitude. Evidence access: Primary abstract Cucurbitacin B Down-Regulates TNF Receptor 1 Expression and Inhibits the TNF-α-Dependent Nuclear Factor κB Signaling Pathway in Human Lung Adenocarcinoma A549 Cells. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35806134/ · DOI 10.3390/ijms23137130
Complete structured claim and evidence
Cucurbitacin B exposure decreased GPX4 protein expression in the human nasopharyngeal-cancer experiments.
Cucurbitacin B → GPX4 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human nasopharyngeal-cancer cells; animal tumor work also reported.
limitations
Expression is not direct GPX4 binding or evidence of selenium depletion.
nutrient_topic
Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Cucurbitacins
plain_language
A lipid-peroxide defense protein decreased in this model.
primary_references
Induction of ferroptosis in human nasopharyngeal cancer cells by cucurbitacin B: molecular mechanism and therapeutic potential. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33664249/ · DOI 10.1038/s41419-021-03516-y
Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 244–250
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human nasopharyngeal-cancer cells; animal tumor work also reported. · source_derived_draft · unverified_draft
## cucurbitacin-b-gpx4-expression A lipid-peroxide defense protein decreased in this model. Cucurbitacin B exposure decreased GPX4 protein expression in the human nasopharyngeal-cancer experiments. Model: Human nasopharyngeal-cancer cells; animal tumor work also reported. Limitations: Expression is not direct GPX4 binding or evidence of selenium depletion. Evidence access: Primary abstract Induction of ferroptosis in human nasopharyngeal cancer cells by cucurbitacin B: molecular mechanism and therapeutic potential. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33664249/ · DOI 10.1038/s41419-021-03516-y
Complete structured claim and evidence
In human H358 and A549 cells, deferoxamine, ferrostatin-1 and liproxstatin-1 reversed cucurbitacin B growth inhibition, supporting a ferroptotic component.
Cucurbitacin B → Human NSCLC ferroptotic response during cucurbitacin B exposure source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human NSCLC cell experiments.
limitations
Rescue does not establish exclusive cell-death causation or clinical cancer efficacy.
nutrient_topic
Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Cucurbitacins
plain_language
Iron chelation and lipid-radical inhibitors changed the outcome.
primary_references
Cucurbitacin B targets STAT3 to induce ferroptosis in non-small cell lung cancer. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38950838/ · DOI 10.1016/j.ejphar.2024.176805
Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 252–258
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human NSCLC cell experiments. · source_derived_draft · unverified_draft
## cucurbitacin-b-ferroptosis-rescue Iron chelation and lipid-radical inhibitors changed the outcome. In human H358 and A549 cells, deferoxamine, ferrostatin-1 and liproxstatin-1 reversed cucurbitacin B growth inhibition, supporting a ferroptotic component. Model: Human NSCLC cell experiments. Limitations: Rescue does not establish exclusive cell-death causation or clinical cancer efficacy. Evidence access: Primary abstract Cucurbitacin B targets STAT3 to induce ferroptosis in non-small cell lung cancer. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38950838/ · DOI 10.1016/j.ejphar.2024.176805
Complete structured claim and evidence
Cucurbitacin B increased lipid ROS, malondialdehyde and measured ferrous iron while lowering glutathione in H358 and A549 experiments.
Cucurbitacin B → Human cancer-cell lipid peroxidation during cucurbitacin B exposure source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human NSCLC experiments; concentration and duration unavailable in accessed abstract.
limitations
Associated readouts do not by themselves order iron release, glutathione loss and lipid oxidation.
nutrient_topic
Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Cucurbitacins
plain_language
Iron and antioxidant balance changed together with membrane damage.
primary_references
Cucurbitacin B targets STAT3 to induce ferroptosis in non-small cell lung cancer. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38950838/ · DOI 10.1016/j.ejphar.2024.176805
Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 260–266
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human NSCLC experiments; concentration and duration unavailable in accessed abstract. · source_derived_draft · unverified_draft
## cucurbitacin-b-lipid-iron Iron and antioxidant balance changed together with membrane damage. Cucurbitacin B increased lipid ROS, malondialdehyde and measured ferrous iron while lowering glutathione in H358 and A549 experiments. Model: Human NSCLC experiments; concentration and duration unavailable in accessed abstract. Limitations: Associated readouts do not by themselves order iron release, glutathione loss and lipid oxidation. Evidence access: Primary abstract Cucurbitacin B targets STAT3 to induce ferroptosis in non-small cell lung cancer. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38950838/ · DOI 10.1016/j.ejphar.2024.176805
Complete structured claim and evidence
Docking and cellular thermal-shift experiments supported STAT3 target engagement by cucurbitacin B, alongside reduced STAT3 phosphorylation.
Cucurbitacin B → STAT3 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human NSCLC study with docking and CETSA.
limitations
CETSA is not purified binding kinetics or proof that STAT3 is the sole or selective target.
nutrient_topic
Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Cucurbitacins
plain_language
The paper tested target engagement as well as signaling.
primary_references
Cucurbitacin B targets STAT3 to induce ferroptosis in non-small cell lung cancer. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38950838/ · DOI 10.1016/j.ejphar.2024.176805
Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 268–274
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human NSCLC study with docking and CETSA. · source_derived_draft · unverified_draft
## cucurbitacin-b-stat3-engagement The paper tested target engagement as well as signaling. Docking and cellular thermal-shift experiments supported STAT3 target engagement by cucurbitacin B, alongside reduced STAT3 phosphorylation. Model: Human NSCLC study with docking and CETSA. Limitations: CETSA is not purified binding kinetics or proof that STAT3 is the sole or selective target. Evidence access: Primary abstract Cucurbitacin B targets STAT3 to induce ferroptosis in non-small cell lung cancer. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38950838/ · DOI 10.1016/j.ejphar.2024.176805
Complete structured claim and evidence
STAT3 overexpression reversed tested cucurbitacin B-associated lipid ROS and iron changes, whereas STAT3 silencing enhanced them.
STAT3 → Human cancer-cell lipid peroxidation during cucurbitacin B exposure source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Human H358/A549 genetic perturbation experiments.
limitations
This establishes model-specific pathway involvement, not universal STAT3 control of ferroptosis.
nutrient_topic
Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Cucurbitacins
plain_language
Changing a signaling protein altered the iron-dependent response.
primary_references
Cucurbitacin B targets STAT3 to induce ferroptosis in non-small cell lung cancer. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38950838/ · DOI 10.1016/j.ejphar.2024.176805
trigger_kind
machinery_impairment Imported condition classification; unverified.
Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 276–282
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human H358/A549 genetic perturbation experiments. · source_derived_draft · unverified_draft
## cucurbitacin-b-stat3-rescue Changing a signaling protein altered the iron-dependent response. STAT3 overexpression reversed tested cucurbitacin B-associated lipid ROS and iron changes, whereas STAT3 silencing enhanced them. Model: Human H358/A549 genetic perturbation experiments. Limitations: This establishes model-specific pathway involvement, not universal STAT3 control of ferroptosis. Evidence access: Primary abstract Cucurbitacin B targets STAT3 to induce ferroptosis in non-small cell lung cancer. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38950838/ · DOI 10.1016/j.ejphar.2024.176805
Complete structured claim and evidence
Docking and CETSA supported an interaction between cucurbitacin B and TLR4 in the NSCLC study.
Cucurbitacin B → Human toll-like receptor 4 / TLR4 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human NSCLC cell experiments with animal tumor models in the same paper.
limitations
No purified affinity or exclusive target assignment follows from docking plus CETSA.
nutrient_topic
Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Cucurbitacins
plain_language
Another proposed target was tested in cells.
primary_references
Cucurbitacin B inhibits non-small cell lung cancer in vivo and in vitro by triggering TLR4/NLRP3/GSDMD-dependent pyroptosis. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34217831/ · DOI 10.1016/j.phrs.2021.105748
Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 284–290
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human NSCLC cell experiments with animal tumor models in the same paper. · source_derived_draft · unverified_draft
## cucurbitacin-b-tlr4-engagement Another proposed target was tested in cells. Docking and CETSA supported an interaction between cucurbitacin B and TLR4 in the NSCLC study. Model: Human NSCLC cell experiments with animal tumor models in the same paper. Limitations: No purified affinity or exclusive target assignment follows from docking plus CETSA. Evidence access: Primary abstract Cucurbitacin B inhibits non-small cell lung cancer in vivo and in vitro by triggering TLR4/NLRP3/GSDMD-dependent pyroptosis. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34217831/ · DOI 10.1016/j.phrs.2021.105748
Complete structured claim and evidence
TLR4 silencing reduced cucurbitacin B-induced pyroptosis and associated mitochondrial ROS and calcium signals in human NSCLC cells.
Human toll-like receptor 4 / TLR4 → Human NSCLC pyroptotic response during cucurbitacin B exposure source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Human NSCLC loss-of-function experiments.
limitations
The accessed abstract does not establish the calcium store or channel; oral calcium depletion is not implied.
nutrient_topic
Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Cucurbitacins
plain_language
Removing the receptor weakened the tested death pathway.
primary_references
Cucurbitacin B inhibits non-small cell lung cancer in vivo and in vitro by triggering TLR4/NLRP3/GSDMD-dependent pyroptosis. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34217831/ · DOI 10.1016/j.phrs.2021.105748
trigger_kind
machinery_impairment Imported condition classification; unverified.
Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 292–298
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human NSCLC loss-of-function experiments. · source_derived_draft · unverified_draft
## cucurbitacin-b-tlr4-loss Removing the receptor weakened the tested death pathway. TLR4 silencing reduced cucurbitacin B-induced pyroptosis and associated mitochondrial ROS and calcium signals in human NSCLC cells. Model: Human NSCLC loss-of-function experiments. Limitations: The accessed abstract does not establish the calcium store or channel; oral calcium depletion is not implied. Evidence access: Primary abstract Cucurbitacin B inhibits non-small cell lung cancer in vivo and in vitro by triggering TLR4/NLRP3/GSDMD-dependent pyroptosis. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34217831/ · DOI 10.1016/j.phrs.2021.105748
Complete structured claim and evidence
Cucurbitacin B exposure was associated with the TLR4/mitochondrial-ROS/NLRP3 route and gasdermin D cleavage in the NSCLC pyroptosis experiments.
Cucurbitacin B → Human NSCLC pyroptotic response during cucurbitacin B exposure source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human NSCLC cells; mouse tumor experiments provide a separate translational level.
limitations
Do not merge all tumor-cell death into one obligatory linear chain.
nutrient_topic
Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Cucurbitacins
plain_language
Inflammatory membrane rupture is separate from ferroptotic lipid damage.
primary_references
Cucurbitacin B inhibits non-small cell lung cancer in vivo and in vitro by triggering TLR4/NLRP3/GSDMD-dependent pyroptosis. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34217831/ · DOI 10.1016/j.phrs.2021.105748
Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 300–306
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human NSCLC cells; mouse tumor experiments provide a separate translational level. · source_derived_draft · unverified_draft
## cucurbitacin-b-pyroptosis-route Inflammatory membrane rupture is separate from ferroptotic lipid damage. Cucurbitacin B exposure was associated with the TLR4/mitochondrial-ROS/NLRP3 route and gasdermin D cleavage in the NSCLC pyroptosis experiments. Model: Human NSCLC cells; mouse tumor experiments provide a separate translational level. Limitations: Do not merge all tumor-cell death into one obligatory linear chain. Evidence access: Primary abstract Cucurbitacin B inhibits non-small cell lung cancer in vivo and in vitro by triggering TLR4/NLRP3/GSDMD-dependent pyroptosis. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34217831/ · DOI 10.1016/j.phrs.2021.105748
Complete structured claim and evidence
Cucurbitacin D at 0.1–1 micromolar reduced glucose uptake and lactate output in human PC3 and DU145 experiments.
Cucurbitacin D → Human prostate-cancer glucose uptake during cucurbitacin D exposure source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human prostate-cancer cell experiments; xenografts also studied.
limitations
Not evidence of effective or safe diabetes treatment.
nutrient_topic
Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Cucurbitacins
plain_language
Fuel handling changed in these cancer cells.
primary_references
Cucurbitacin D Reprograms Glucose Metabolic Network in Prostate Cancer. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30875788/ · DOI 10.3390/cancers11030364
Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 308–314
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human prostate-cancer cell experiments; xenografts also studied. · source_derived_draft · unverified_draft
## cucurbitacin-d-glucose Fuel handling changed in these cancer cells. Cucurbitacin D at 0.1–1 micromolar reduced glucose uptake and lactate output in human PC3 and DU145 experiments. Model: Human prostate-cancer cell experiments; xenografts also studied. Limitations: Not evidence of effective or safe diabetes treatment. Evidence access: Primary abstract Cucurbitacin D Reprograms Glucose Metabolic Network in Prostate Cancer. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30875788/ · DOI 10.3390/cancers11030364
Complete structured claim and evidence
Cucurbitacin D decreased GLUT1 expression in the prostate-cancer study; miR-132-associated changes were also reported.
Cucurbitacin D → Human glucose transporter 1 / SLC2A1 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human PC3/DU145 cells and xenograft work.
limitations
Expression and correlated microRNA changes do not establish a single exclusive mechanism.
nutrient_topic
Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Cucurbitacins
plain_language
Transporter abundance offers one route to altered glucose handling.
primary_references
Cucurbitacin D Reprograms Glucose Metabolic Network in Prostate Cancer. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30875788/ · DOI 10.3390/cancers11030364
Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 316–322
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human PC3/DU145 cells and xenograft work. · source_derived_draft · unverified_draft
## cucurbitacin-d-glut1-expression Transporter abundance offers one route to altered glucose handling. Cucurbitacin D decreased GLUT1 expression in the prostate-cancer study; miR-132-associated changes were also reported. Model: Human PC3/DU145 cells and xenograft work. Limitations: Expression and correlated microRNA changes do not establish a single exclusive mechanism. Evidence access: Primary abstract Cucurbitacin D Reprograms Glucose Metabolic Network in Prostate Cancer. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30875788/ · DOI 10.3390/cancers11030364
Complete structured claim and evidence
Molecular docking proposed cucurbitacin D binding to GLUT1.
Cucurbitacin D → Human glucose transporter 1 / SLC2A1 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Computational docking within the glucose-metabolism study.
limitations
No transporter-binding kinetics or reconstituted transport-inhibition measurement was established by docking.
nutrient_topic
Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Cucurbitacins
plain_language
Direct transporter binding remains a prediction in this evidence record.
primary_references
Cucurbitacin D Reprograms Glucose Metabolic Network in Prostate Cancer. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30875788/ · DOI 10.3390/cancers11030364
Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 324–330
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Computational docking within the glucose-metabolism study. · source_derived_draft · unverified_draft
## cucurbitacin-d-glut1-docking Direct transporter binding remains a prediction in this evidence record. Molecular docking proposed cucurbitacin D binding to GLUT1. Model: Computational docking within the glucose-metabolism study. Limitations: No transporter-binding kinetics or reconstituted transport-inhibition measurement was established by docking. Evidence access: Primary abstract Cucurbitacin D Reprograms Glucose Metabolic Network in Prostate Cancer. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30875788/ · DOI 10.3390/cancers11030364
Complete structured claim and evidence
Cucurbitacin D interfered with EGF–EGFR binding in a solid-phase binding assay and reduced EGFR phosphorylation in the NSCLC study.
Cucurbitacin D → Epidermal growth factor receptor source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Binding assay and gefitinib-resistant human NSCLC cell models.
limitations
This does not establish a clinically effective replacement for an EGFR inhibitor.
nutrient_topic
Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Cucurbitacins
plain_language
A growth-factor interaction was tested upstream of signaling.
primary_references
Cucurbitacin D Overcomes Gefitinib Resistance by Blocking EGF Binding to EGFR and Inducing Cell Death in NSCLCs. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32133284/ · DOI 10.3389/fonc.2020.00062
Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 332–338
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Binding assay and gefitinib-resistant human NSCLC cell models. · source_derived_draft · unverified_draft
## cucurbitacin-d-egf-binding A growth-factor interaction was tested upstream of signaling. Cucurbitacin D interfered with EGF–EGFR binding in a solid-phase binding assay and reduced EGFR phosphorylation in the NSCLC study. Model: Binding assay and gefitinib-resistant human NSCLC cell models. Limitations: This does not establish a clinically effective replacement for an EGFR inhibitor. Evidence access: Primary abstract Cucurbitacin D Overcomes Gefitinib Resistance by Blocking EGF Binding to EGFR and Inducing Cell Death in NSCLCs. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32133284/ · DOI 10.3389/fonc.2020.00062
Complete structured claim and evidence
Cucurbitacin D enhanced LPS-associated IL-1-beta production and caspase-1-dependent inflammasome activation; the study reported NLRP3–ASC interaction and an ERK-dependent transcription component.
Cucurbitacin D → Cucurbitacin D inflammatory response in human/mouse myeloid study panel source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Panel included human THP-1 and murine RAW264, peritoneal and bone-marrow-derived macrophages; individual assay species unresolved in accessed abstract.
limitations
Mixed-model process is retained explicitly; no individual molecular result is silently assigned to human cells. Different member/stimulus from CuB A549 suppression.
nutrient_topic
Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Cucurbitacins
plain_language
This member increased an inflammatory response under these conditions.
primary_references
Cucurbitacin D is a new inflammasome activator in macrophages. · 2013 · https://pubmed.ncbi.nlm.nih.gov/24140411/ · DOI 10.1016/j.intimp.2013.10.003
Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 340–346
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Panel included human THP-1 and murine RAW264, peritoneal and bone-marrow-derived macrophages; individual assay species unresolved in accessed abstract. · source_derived_draft · unverified_draft
## cucurbitacin-d-inflammasome This member increased an inflammatory response under these conditions. Cucurbitacin D enhanced LPS-associated IL-1-beta production and caspase-1-dependent inflammasome activation; the study reported NLRP3–ASC interaction and an ERK-dependent transcription component. Model: Panel included human THP-1 and murine RAW264, peritoneal and bone-marrow-derived macrophages; individual assay species unresolved in accessed abstract. Limitations: Mixed-model process is retained explicitly; no individual molecular result is silently assigned to human cells. Different member/stimulus from CuB A549 suppression. Evidence access: Primary abstract Cucurbitacin D is a new inflammasome activator in macrophages. · 2013 · https://pubmed.ncbi.nlm.nih.gov/24140411/ · DOI 10.1016/j.intimp.2013.10.003
Complete structured claim and evidence
Male Wistar rats receiving oral cucurbitacin B at 2–4 mg/kg versus intravenous 0.1 mg/kg had estimated oral bioavailability of about 10%, with oral peak around 30 minutes.
Cucurbitacin B → Rat cucurbitacin B oral bioavailability source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
evidence_access
Primary full text PMC6609384
experimental_model
Rat pharmacokinetics, six animals per reported group; clear solution in 40% v/v DMSO.
limitations
Not a human absorption estimate or dosing recommendation.
nutrient_topic
Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Cucurbitacins
plain_language
Oral dose and systemic exposure were far from equivalent.
primary_references
Pharmacokinetics of cucurbitacin B from Trichosanthes cucumerina L. in rats. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31272429/ · DOI 10.1186/s12906-019-2568-7
trigger_kind
biomarker_context Imported condition classification; unverified.
Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 348–354
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat pharmacokinetics, six animals per reported group; clear solution in 40% v/v DMSO. · source_derived_draft · unverified_draft
## cucurbitacin-b-rat-absorption Oral dose and systemic exposure were far from equivalent. Male Wistar rats receiving oral cucurbitacin B at 2–4 mg/kg versus intravenous 0.1 mg/kg had estimated oral bioavailability of about 10%, with oral peak around 30 minutes. Model: Rat pharmacokinetics, six animals per reported group; clear solution in 40% v/v DMSO. Limitations: Not a human absorption estimate or dosing recommendation. Evidence access: Primary full text PMC6609384 Pharmacokinetics of cucurbitacin B from Trichosanthes cucumerina L. in rats. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31272429/ · DOI 10.1186/s12906-019-2568-7
Complete structured claim and evidence
The rat study estimated intravenous distribution volume near 51.65 L/kg ; lung and spleen tissue/plasma ratios were about 60 at 1 hour and about 240 at 2 hours, while liver, stomach and small intestine ratios were only 4–14 at 1 hour.
Cucurbitacin B → Rat cucurbitacin B tissue distribution source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
evidence_access
Primary full text PMC6609384
experimental_model
Male Wistar rat intravenous pharmacokinetics and tissue sampling; brain and heart amounts were below quantification.
limitations
Total tissue ratios do not establish free intracellular concentration or a human therapeutic window.
nutrient_topic
Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Cucurbitacins
plain_language
Measured tissue distribution differed substantially from plasma.
primary_references
Pharmacokinetics of cucurbitacin B from Trichosanthes cucumerina L. in rats. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31272429/ · DOI 10.1186/s12906-019-2568-7
trigger_kind
biomarker_context Imported condition classification; unverified.
Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 356–362
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Male Wistar rat intravenous pharmacokinetics and tissue sampling; brain and heart amounts were below quantification. · source_derived_draft · unverified_draft
## cucurbitacin-b-rat-distribution Measured tissue distribution differed substantially from plasma. The rat study estimated intravenous distribution volume near 51.65 L/kg ; lung and spleen tissue/plasma ratios were about 60 at 1 hour and about 240 at 2 hours, while liver, stomach and small intestine ratios were only 4–14 at 1 hour. Model: Male Wistar rat intravenous pharmacokinetics and tissue sampling; brain and heart amounts were below quantification. Limitations: Total tissue ratios do not establish free intracellular concentration or a human therapeutic window. Evidence access: Primary full text PMC6609384 Pharmacokinetics of cucurbitacin B from Trichosanthes cucumerina L. in rats. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31272429/ · DOI 10.1186/s12906-019-2568-7
Complete structured claim and evidence
Rat cucurbitacin B metabolism profiling detected a cysteine conjugate among phase-II products; 13 metabolites were identified and seven confirmed in the overall study.
Cucurbitacin B → Cucurbitacin B cysteine conjugate source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Rat LC-MS metabolism study.
limitations
Not all structures had identical confirmation strength; this record does not infer human rates.
nutrient_topic
Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Cucurbitacins
plain_language
Cysteine also appears in a measured metabolic product.
primary_references
Metabolic fate of the natural anticancer agent cucurbitacin B: an LC-MS/MS-enabled profiling of its major phase I and II conjugates in vivo. · 2024 · https://pubmed.ncbi.nlm.nih.gov/39441433/ · DOI 10.1007/s00216-024-05608-y
Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 364–370
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat LC-MS metabolism study. · source_derived_draft · unverified_draft
## cucurbitacin-b-rat-cysteine-metabolism Cysteine also appears in a measured metabolic product. Rat cucurbitacin B metabolism profiling detected a cysteine conjugate among phase-II products; 13 metabolites were identified and seven confirmed in the overall study. Model: Rat LC-MS metabolism study. Limitations: Not all structures had identical confirmation strength; this record does not infer human rates. Evidence access: Primary abstract Metabolic fate of the natural anticancer agent cucurbitacin B: an LC-MS/MS-enabled profiling of its major phase I and II conjugates in vivo. · 2024 · https://pubmed.ncbi.nlm.nih.gov/39441433/ · DOI 10.1007/s00216-024-05608-y
Complete structured claim and evidence
Rat cucurbitacin B metabolism profiling identified glutathione conjugation among the phase-II routes.
Cucurbitacin B → Cucurbitacin B glutathione conjugate source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Rat LC-MS study; also hydrolysis, reduction, epoxidation, amination and other conjugation routes reported.
limitations
No human mass balance or obligatory single detoxification pathway was established.
nutrient_topic
Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Cucurbitacins
plain_language
The existing glutathione node connects chemical interception to metabolism.
primary_references
Metabolic fate of the natural anticancer agent cucurbitacin B: an LC-MS/MS-enabled profiling of its major phase I and II conjugates in vivo. · 2024 · https://pubmed.ncbi.nlm.nih.gov/39441433/ · DOI 10.1007/s00216-024-05608-y
Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 372–378
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat LC-MS study; also hydrolysis, reduction, epoxidation, amination and other conjugation routes reported. · source_derived_draft · unverified_draft
## cucurbitacin-b-rat-gsh-metabolism The existing glutathione node connects chemical interception to metabolism. Rat cucurbitacin B metabolism profiling identified glutathione conjugation among the phase-II routes. Model: Rat LC-MS study; also hydrolysis, reduction, epoxidation, amination and other conjugation routes reported. Limitations: No human mass balance or obligatory single detoxification pathway was established. Evidence access: Primary abstract Metabolic fate of the natural anticancer agent cucurbitacin B: an LC-MS/MS-enabled profiling of its major phase I and II conjugates in vivo. · 2024 · https://pubmed.ncbi.nlm.nih.gov/39441433/ · DOI 10.1007/s00216-024-05608-y
Complete structured claim and evidence
The cucurbitacin B cysteine conjugate retained antiproliferative activity in tested HepG2, MCF7 and PANC1 cells.
Cucurbitacin B cysteine conjugate → Human cancer-cell proliferation during CuB-cysteine conjugate exposure source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human cancer-cell models of an identified metabolite.
limitations
Not evidence of clinical efficacy or selectivity for cancer over authenticated normal cells.
nutrient_topic
Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Cucurbitacins
plain_language
Conjugation did not automatically erase every biological effect.
primary_references
Metabolic fate of the natural anticancer agent cucurbitacin B: an LC-MS/MS-enabled profiling of its major phase I and II conjugates in vivo. · 2024 · https://pubmed.ncbi.nlm.nih.gov/39441433/ · DOI 10.1007/s00216-024-05608-y
Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 380–386
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cancer-cell models of an identified metabolite. · source_derived_draft · unverified_draft
## cucurbitacin-b-cys-retained-activity Conjugation did not automatically erase every biological effect. The cucurbitacin B cysteine conjugate retained antiproliferative activity in tested HepG2, MCF7 and PANC1 cells. Model: Human cancer-cell models of an identified metabolite. Limitations: Not evidence of clinical efficacy or selectivity for cancer over authenticated normal cells. Evidence access: Primary abstract Metabolic fate of the natural anticancer agent cucurbitacin B: an LC-MS/MS-enabled profiling of its major phase I and II conjugates in vivo. · 2024 · https://pubmed.ncbi.nlm.nih.gov/39441433/ · DOI 10.1007/s00216-024-05608-y
Complete structured claim and evidence
At equal oral formulation doses, nanosuspension increased measured peak concentration and exposure area for cucurbitacins B, D and E in rats.
Rat oral cucurbitacin nanosuspension formulation → Cucurbitacin B source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
2025 rat pharmacokinetic formulation comparison; dose not specified in accessed abstract.
limitations
Does not establish human bioavailability or improved clinical safety.
nutrient_topic
Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Cucurbitacins
plain_language
Changing the formulation changed exposure to each member.
primary_references
Comparison of the pharmacokinetic profiles of three triterpenoids after oral administration of a cucurbitacin tablet and nanosuspension by UHPLC-MS/MS. · 2025 · https://pubmed.ncbi.nlm.nih.gov/41001343/ · DOI 10.3389/fphar.2025.1647015
trigger_kind
biomarker_context Imported condition classification; unverified.
Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 388–394
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · 2025 rat pharmacokinetic formulation comparison; dose not specified in accessed abstract. · source_derived_draft · unverified_draft
## cucurbitacin-formulation-exposure Changing the formulation changed exposure to each member. At equal oral formulation doses, nanosuspension increased measured peak concentration and exposure area for cucurbitacins B, D and E in rats. Model: 2025 rat pharmacokinetic formulation comparison; dose not specified in accessed abstract. Limitations: Does not establish human bioavailability or improved clinical safety. Evidence access: Primary abstract Comparison of the pharmacokinetic profiles of three triterpenoids after oral administration of a cucurbitacin tablet and nanosuspension by UHPLC-MS/MS. · 2025 · https://pubmed.ncbi.nlm.nih.gov/41001343/ · DOI 10.3389/fphar.2025.1647015
Complete structured claim and evidence
In 353 French poison-center cases involving non-edible squash, 204 were symptomatic, predominantly with gastrointestinal effects; the series included dehydration or hypotension and recorded no severe cases or deaths.
Human bitter-squash mixture exposure → Human bitter-squash gastrointestinal poisoning source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human retrospective poison-center series; compound mixture, individual cucurbitacin identity and dose unmeasured.
limitations
Case-series selection and unquantified mixtures prevent member-specific dose-response inference; absence of deaths in this series is not universal safety.
nutrient_topic
Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Cucurbitacins
plain_language
Human exposure evidence includes poisoning, not just experimental anticancer effects.
primary_references
Poisoning by non-edible squash: retrospective series of 353 patients from French Poison Control Centers. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29323540/ · DOI 10.1080/15563650.2018.1424891
Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 396–402
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human retrospective poison-center series; compound mixture, individual cucurbitacin identity and dose unmeasured. · source_derived_draft · unverified_draft
## cucurbitacin-human-bitter-squash Human exposure evidence includes poisoning, not just experimental anticancer effects. In 353 French poison-center cases involving non-edible squash, 204 were symptomatic, predominantly with gastrointestinal effects; the series included dehydration or hypotension and recorded no severe cases or deaths. Model: Human retrospective poison-center series; compound mixture, individual cucurbitacin identity and dose unmeasured. Limitations: Case-series selection and unquantified mixtures prevent member-specific dose-response inference; absence of deaths in this series is not universal safety. Evidence access: Primary abstract Poisoning by non-edible squash: retrospective series of 353 patients from French Poison Control Centers. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29323540/ · DOI 10.1080/15563650.2018.1424891
Complete structured claim and evidence
Glutamate-cysteine ligase joins glutamate and cysteine to form gamma-glutamylcysteine in the first glutathione-synthesis step.
Human glutamate-cysteine ligase catalytic subunit / GCLC → Gamma-glutamylcysteine source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/sulforaphane-research/30581542.fulltext.txt", "locator": "Primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "77cf6674cf9b9bc140a228588a53c937966fd3a67397c1c4970221c5cc58a0b1", "start_char": 762, "end_char": 1092, "text_sha256": "927fa13b085700c20b578ecabc7c8c17a66ea4600b90809e3061d12bcaea3849"}
experimental_model
Human enzyme mutagenesis, kinetics and molecular dynamics
exposure
S-loop variants; established biosynthetic reactions described in the introduction
limitations
Reaction descriptions are background chemistry in a primary enzyme paper, not evidence that sulforaphane corrects inherited GSS deficiency.
nutrient_topic
Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. · Sulforaphane / SFN, stereochemistry specified per study
organism
Human GSS
plain_language
The induced machinery still needs its amino-acid building blocks.
primary_references
[sulforaphane-p30581542] Genetic Mutations in the S-loop of Human Glutathione Synthetase: Links Between Substrate Binding, Active Site Structure and Allostery. (2019). https://pubmed.ncbi.nlm.nih.gov/30581542/ DOI: 10.1016/j.csbj.2018.11.008
tissue_or_cell_type
Glutathione synthesis and substrate binding
Sulforaphane: formation, electrophile sensing and nutrient connections (2026-09-17) · lines 840–851
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human enzyme mutagenesis, kinetics and molecular dynamics · source_derived_draft · unverified_draft
### sulforaphane-gcl-first-step Glutamate-cysteine ligase joins glutamate and cysteine to form gamma-glutamylcysteine in the first glutathione-synthesis step. Condition category: normal nutrient_topic: Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. plain_language: The induced machinery still needs its amino-acid building blocks. organism: Human GSS tissue_or_cell_type: Glutathione synthesis and substrate binding experimental_model: Human enzyme mutagenesis, kinetics and molecular dynamics limitations: Reaction descriptions are background chemistry in a primary enzyme paper, not evidence that sulforaphane corrects inherited GSS deficiency. exposure: S-loop variants; established biosynthetic reactions described in the introduction evidence_span: {"source_cache": "artifacts/sulforaphane-research/30581542.fulltext.txt", "locator": "Primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "77cf6674cf9b9bc140a228588a53c937966fd3a67397c1c4970221c5cc58a0b1", "start_char": 762, "end_char": 1092, "text_sha256": "927fa13b085700c20b578ecabc7c8c17a66ea4600b90809e3061d12bcaea3849"} [sulforaphane-p30581542] Genetic Mutations in the S-loop of Human Glutathione Synthetase: Links Between Substrate Binding, Active Site Structure and Allostery. (2019). https://pubmed.ncbi.nlm.nih.gov/30581542/ DOI: 10.1016/j.csbj.2018.11.008
Complete structured claim and evidence
Purified PHGPX (GPX4) with glutathione reduced phospholipid hydroperoxides within photooxidized human erythrocyte ghost membranes to alcohol products without prior phospholipase cleavage.
GPX4 → Phospholipid hydroperoxides source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
evidence_location
Primary abstract
experimental_model
Rose-bengal photoperoxidation followed by enzyme treatment
exposure
GSH/PHGPX after photooxidation.
limitations
Purified-enzyme preparation; distinguishes peroxide removal from vitamin E radical trapping.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Human-derived cell-free membranes
plain_language
GPX4 removed peroxide groups from membrane phospholipids using glutathione.
primary_references
[ver-thomas1990] Protective action of phospholipid hydroperoxide glutathione peroxidase against membrane-damaging lipid peroxidation. In situ reduction of phospholipid and cholesterol hydroperoxides. (1990). https://pubmed.ncbi.nlm.nih.gov/2294113/ DOI: 10.1016/s0021-9258(19)40252-4
tissue_or_cell_type
Erythrocyte ghosts
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 550–562
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rose-bengal photoperoxidation followed by enzyme treatment · source_derived_draft · unverified_draft
### ver-gpx4-pl-hydroperoxide-reduction Purified PHGPX (GPX4) with glutathione reduced phospholipid hydroperoxides within photooxidized human erythrocyte ghost membranes to alcohol products without prior phospholipase cleavage. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: GPX4 removed peroxide groups from membrane phospholipids using glutathione. organism: Human-derived cell-free membranes tissue_or_cell_type: Erythrocyte ghosts experimental_model: Rose-bengal photoperoxidation followed by enzyme treatment limitations: Purified-enzyme preparation; distinguishes peroxide removal from vitamin E radical trapping. exposure: GSH/PHGPX after photooxidation. cross_nutrient: true evidence_location: Primary abstract [ver-thomas1990] Protective action of phospholipid hydroperoxide glutathione peroxidase against membrane-damaging lipid peroxidation. In situ reduction of phospholipid and cholesterol hydroperoxides. (1990). https://pubmed.ncbi.nlm.nih.gov/2294113/ DOI: 10.1016/s0021-9258(19)40252-4
Complete structured claim and evidence
At a physiological vitamin E-to-phospholipid ratio, inhibition of iron-dependent lipid peroxidation in rat liver microsomes and dispersed microsomal lipids was observed only when PHGPX (GPX4) and glutathione were also present.
Alpha-tocopherol → Lipid peroxidation source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
evidence_location
Primary abstract
experimental_model
Microsomes and Triton-dispersed lipid micelles
exposure
Iron-dependent peroxidation; physiological vitamin E:phospholipid ratio as reported in abstract.
limitations
Exact concentrations are not available in the inspected abstract. Model-specific dependence does not imply every membrane requires added GPX4 to show E protection.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Rattus norvegicus
plain_language
Vitamin E protection depended on peroxide removal by the GPX4/glutathione system in these preparations.
primary_references
[ver-maiorino1989] Microsomal lipid peroxidation: effect of vitamin E and its functional interaction with phospholipid hydroperoxide glutathione peroxidase. (1989). https://pubmed.ncbi.nlm.nih.gov/2586229/ DOI: 10.1007/bf02535211
tissue_or_cell_type
Liver microsomal lipids
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 592–604
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Microsomes and Triton-dispersed lipid micelles · source_derived_draft · unverified_draft
### ver-gpx4-gsh-tocopherol-cooperation At a physiological vitamin E-to-phospholipid ratio, inhibition of iron-dependent lipid peroxidation in rat liver microsomes and dispersed microsomal lipids was observed only when PHGPX (GPX4) and glutathione were also present. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin E protection depended on peroxide removal by the GPX4/glutathione system in these preparations. organism: Rattus norvegicus tissue_or_cell_type: Liver microsomal lipids experimental_model: Microsomes and Triton-dispersed lipid micelles limitations: Exact concentrations are not available in the inspected abstract. Model-specific dependence does not imply every membrane requires added GPX4 to show E protection. exposure: Iron-dependent peroxidation; physiological vitamin E:phospholipid ratio as reported in abstract. cross_nutrient: true evidence_location: Primary abstract [ver-maiorino1989] Microsomal lipid peroxidation: effect of vitamin E and its functional interaction with phospholipid hydroperoxide glutathione peroxidase. (1989). https://pubmed.ncbi.nlm.nih.gov/2586229/ DOI: 10.1007/bf02535211
Complete structured claim and evidence
Maternal dietary supplementation with 500 IU/kg DL-alpha-tocopheryl acetate through gestation and nursing allowed Alb-Cre;Gpx4fl/fl pups to survive to weaning, whereas liver-specific Gpx4-null pups on standard chow died within 48 hours after birth.
All-rac-alpha-tocopheryl acetate → Hepatocyte-directed GPX4 loss source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
true
evidence_location
Results/Table 2; standard-chow comparison Table 1
experimental_model
Alb-Cre conditional Gpx4 deletion and maternal diet
exposure
500 IU/kg DL-alpha-tocopheryl acetate during gestation/lactation; weaning at 3 weeks.
limitations
Alb-Cre Gpx4 loss is machinery impairment, not selenium deficiency; mouse survival rescue does not establish human substitutability.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Mus musculus
plain_language
Extra dietary vitamin E rescued early survival in mice lacking liver GPX4.
primary_references
[ver-carlson2016] Glutathione peroxidase 4 and vitamin E cooperatively prevent hepatocellular degeneration. (2016). https://pubmed.ncbi.nlm.nih.gov/27262435/ DOI: 10.1016/j.redox.2016.05.003
tissue_or_cell_type
Hepatocytes and whole-animal survival
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 606–618
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Alb-Cre conditional Gpx4 deletion and maternal diet · source_derived_draft · unverified_draft
### ver-liver-gpx4-e-rescue Maternal dietary supplementation with 500 IU/kg DL-alpha-tocopheryl acetate through gestation and nursing allowed Alb-Cre;Gpx4fl/fl pups to survive to weaning, whereas liver-specific Gpx4-null pups on standard chow died within 48 hours after birth. Condition category: machinery_impairment nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Extra dietary vitamin E rescued early survival in mice lacking liver GPX4. organism: Mus musculus tissue_or_cell_type: Hepatocytes and whole-animal survival experimental_model: Alb-Cre conditional Gpx4 deletion and maternal diet limitations: Alb-Cre Gpx4 loss is machinery impairment, not selenium deficiency; mouse survival rescue does not establish human substitutability. exposure: 500 IU/kg DL-alpha-tocopheryl acetate during gestation/lactation; weaning at 3 weeks. cross_nutrient: true evidence_location: Results/Table 2; standard-chow comparison Table 1 [ver-carlson2016] Glutathione peroxidase 4 and vitamin E cooperatively prevent hepatocellular degeneration. (2016). https://pubmed.ncbi.nlm.nih.gov/27262435/ DOI: 10.1016/j.redox.2016.05.003
Complete structured claim and evidence
After six weeks on vitamin E-enriched diets, switching liver-specific Gpx4-null mice to vitamin E-deficient diet caused extensive hepatocellular necrosis and loss of the prior survival rescue; control genotypes survived the monitored 78 days after withdrawal.
Hepatocyte-directed GPX4 loss → Hepatocyte necrosis source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
true
evidence_location
Figures 4–5
experimental_model
Diet withdrawal after developmental rescue
exposure
E-enriched diet through 6 weeks; subsequent E withdrawal; necrosis examined after 3 weeks.
limitations
Alb-Cre Gpx4 loss is machinery impairment, not selenium deficiency; mouse survival rescue does not establish human substitutability.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Mus musculus
plain_language
The rescued mice remained dependent on continued vitamin E supply.
primary_references
[ver-carlson2016] Glutathione peroxidase 4 and vitamin E cooperatively prevent hepatocellular degeneration. (2016). https://pubmed.ncbi.nlm.nih.gov/27262435/ DOI: 10.1016/j.redox.2016.05.003
tissue_or_cell_type
Liver
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 620–632
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Diet withdrawal after developmental rescue · source_derived_draft · unverified_draft
### ver-liver-gpx4-e-withdrawal After six weeks on vitamin E-enriched diets, switching liver-specific Gpx4-null mice to vitamin E-deficient diet caused extensive hepatocellular necrosis and loss of the prior survival rescue; control genotypes survived the monitored 78 days after withdrawal. Condition category: nutrient_deficiency nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: The rescued mice remained dependent on continued vitamin E supply. organism: Mus musculus tissue_or_cell_type: Liver experimental_model: Diet withdrawal after developmental rescue limitations: Alb-Cre Gpx4 loss is machinery impairment, not selenium deficiency; mouse survival rescue does not establish human substitutability. exposure: E-enriched diet through 6 weeks; subsequent E withdrawal; necrosis examined after 3 weeks. cross_nutrient: true evidence_location: Figures 4–5 [ver-carlson2016] Glutathione peroxidase 4 and vitamin E cooperatively prevent hepatocellular degeneration. (2016). https://pubmed.ncbi.nlm.nih.gov/27262435/ DOI: 10.1016/j.redox.2016.05.003
Complete structured claim and evidence
Another defense changes how vulnerable cells are to GPX4 loss.
FSP1 reduces CoQ and supplies a lipid-radical defense operating in parallel with GPX4.
FSP1 → Reduced CoQ10 source_derived_draftliterature_reviewed:direct_experimental
Experimental context and source evidence
cell_type
Experimental cultured cells
experimental_model
Cell genetics and biochemical experiments
limitations
Capacity and dependence vary by cell; not a universal dietary threshold.
organism
Human cell models
Selenium: literature corrections and mechanism additions · lines 1492–1502
Metabolic Ledger literature curation, 17 September 2026; primary papers linked individually · supports · Cell genetics and biochemical experiments · secondary_verified · secondary_verified
## fsp1-parallel Another defense changes how vulnerable cells are to GPX4 loss. FSP1 reduces CoQ and supplies a lipid-radical defense operating in parallel with GPX4. Organism: Human cell models Cell type: Experimental cultured cells Experimental model: Cell genetics and biochemical experiments Limitations: Capacity and dependence vary by cell; not a universal dietary threshold. Primary reference: [The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis](https://www.nature.com/articles/s41586-019-1705-2)
Complete structured claim and evidence
Disrupted selenium uptake hindered GPX4 production in these cancer cells.
LRP8 loss caused GPX4 UGA-associated ribosome stalling in the tested cancer cells.
ApoER2 / LRP8 → Ribosome stalling at GPX4 UGA source_derived_draftliterature_reviewed:direct_experimental
Experimental context and source evidence
cell_type
cancer cell lines
experimental_model
Genetic disruption and ribosome analyses
limitations
Tumor-cell result; GPX4 priority is context dependent.
organism
human
Selenium: literature corrections and mechanism additions · lines 594–604
Metabolic Ledger literature curation, 17 September 2026; primary papers linked individually · supports · Genetic disruption and ribosome analyses · secondary_verified · secondary_verified
## lrp8-loss-promotes-gpx4-stalling Disrupted selenium uptake hindered GPX4 production in these cancer cells. LRP8 loss caused GPX4 UGA-associated ribosome stalling in the tested cancer cells. Organism: human Cell type: cancer cell lines Experimental model: Genetic disruption and ribosome analyses Limitations: Tumor-cell result; GPX4 priority is context dependent. Primary reference: [Ribosome stalling during selenoprotein translation exposes a ferroptosis vulnerability](https://pubmed.ncbi.nlm.nih.gov/35637349/)
Complete structured claim and evidence
Replacing selenium with sulfur retains some function but weakens peroxide resistance.
GPX4 Sec-to-Cys substitution retains context-dependent residual function but increases peroxide-induced inactivation and ferroptosis susceptibility.
GPX4 Sec-to-Cys variant → Ferroptosis source_derived_draftliterature_reviewed:direct_experimental
Experimental context and source evidence
cell_type
Knock-in tissues and derived/engineered cells
experimental_model
Gpx4 Sec-to-Cys knock-in mice, tissue assays and cell peroxide challenges
limitations
Tissue PCOOH activity was undetectable in reported brain/kidney assays; mutation is not nutritional deficiency.
organism
Mus musculus
Selenium: literature corrections and mechanism additions · lines 1263–1273
Metabolic Ledger literature curation, 17 September 2026; primary papers linked individually · supports · Gpx4 Sec-to-Cys knock-in mice, tissue assays and cell peroxide challenges · secondary_verified · secondary_verified
## gpx4-cys-vulnerability Replacing selenium with sulfur retains some function but weakens peroxide resistance. GPX4 Sec-to-Cys substitution retains context-dependent residual function but increases peroxide-induced inactivation and ferroptosis susceptibility. Organism: Mus musculus Cell type: Knock-in tissues and derived/engineered cells Experimental model: Gpx4 Sec-to-Cys knock-in mice, tissue assays and cell peroxide challenges Limitations: Tissue PCOOH activity was undetectable in reported brain/kidney assays; mutation is not nutritional deficiency. Primary reference: [Selenium Utilization by GPX4 Is Required to Prevent Hydroperoxide-Induced Ferroptosis](https://pubmed.ncbi.nlm.nih.gov/29290465/)
Complete structured claim and evidence

Availability and dependencies

Each situation shows the normal role first, then what the sources report under a specific condition. A shortfall in the diet, a fault in the machinery, and a low blood reading are kept separate because they are not the same thing.

Blocking glutathione synthesis increases experimental sensitivity

Condition: machinery_impairment · BSO pretreatment inhibits synthesis.

Normal role: Glutathione contributes to cellular redox and reactive-compound handling.

Recorded consequence: Cucurbitacin B cytotoxicity increases.

Scope: Human NSCLC cells.

STAT3 perturbation has endpoint-specific consequences

Condition: machinery_impairment · STAT3/JAK2 silencing or STAT3 overexpression in different experiments.

Normal role: Signaling and redox routes interact.

Recorded consequence: Rac1 effects were not reproduced by one perturbation, while CuB lipid/iron effects changed in another.

Scope: Different human cancer-cell models and compound members.

Blocking receptor processing changes TNFR1 loss

Condition: machinery_impairment · Pharmacological converting-enzyme inhibition.

Normal role: TNFR1 abundance affects cytokine signaling.

Recorded consequence: Attenuated CuB-associated TNFR1 down-regulation.

Scope: Human A549 cells.

Removing TLR4 weakens the tested pyroptotic route

Condition: machinery_impairment · TLR4 silencing during CuB exposure.

Normal role: TLR4-linked signaling can affect mitochondrial stress.

Recorded consequence: Reduced pyroptosis, ROS and calcium readouts.

Scope: Human NSCLC cells.

Route, tissue and formulation change exposure

Condition: biomarker_context · Oral versus intravenous administration and altered formulation.

Normal role: Compound delivery depends on absorption and distribution.

Recorded consequence: Different circulating and tissue exposure.

Scope: Rat pharmacokinetics.

The sources

Every document behind this chapter is preserved word for word. Open one to read it in full with its recorded conflicts marked in place.

Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20)AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · unverified_draftRead preserved source
Selenium: literature corrections and mechanism additionsMetabolic Ledger literature curation, 17 September 2026; primary papers linked individually · secondary_verifiedRead preserved source
Sulforaphane: formation, electrophile sensing and nutrient connections (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source

Recorded disagreements

Where two sources say different things, both are kept and the difference is explained. You can discuss a disagreement or propose a mechanism that might account for it.

Open questions in this collection

Questions the curators could not answer from the sources in front of them, kept here with the reason each one is still open. These are gaps in this collection, not findings or proof that no one has studied them.

Chapters are assembled from supplied drafts and curated literature summaries. Statements remain unverified against the primary studies, and the ledger is not medical advice.

Evidence, AI assistance and curation standards

Cucurbitacins

The mechanisms

Incubating purified human cofilin 1 with cucurbitacin D produced covalent adducts; mass shifts were compatible with about four compound molecules per cofilin under the tested excess-compound conditions.

Incubating purified human cofilin 1 with cucurbitacin E produced covalent adducts; mass shifts were compatible with about four compound molecules per cofilin under the tested excess-compound conditions.

Incubating purified human cofilin 1 with cucurbitacin I produced covalent adducts; mass shifts were compatible with about four compound molecules per cofilin under the tested excess-compound conditions.

Mass spectrometry localized cucurbitacin E modification to cofilin Cys39, Cys80 and Cys139, with weaker evidence for Cys147.

Cucurbitacin E pretreatment inhibited the F-actin-severing activity of purified human cofilin 1.

Cucurbitacin E covalently modified actin at Cys257 in F-actin and inhibited depolymerization, with effects at substoichiometric compound:actin ratios down to 1:6.

The cucurbitacin E actin study reported binding to filamentous actin but not globular actin.

Adding cucurbitacin I rapidly reduced motility and produced actin aggregates in canine MDCK cells.

In the 2010 purified-actin assays, cucurbitacin I did not change depolymerization rate at concentrations active in cells; high concentrations delayed polymerization initiation without changing its subsequent rate.

Cucurbitacin I at 1–200 nM increased G-actin thermal stability in a thermal-shift assay, supporting an interaction in that preparation.

Adding cucurbitacin I inhibited actin polymerization in the 2024 in-vitro experiment.

Docking and molecular dynamics proposed cucurbitacin I contacts involving actin residues I136, I175, D154 and A138.

UV spectroscopy and FTICR mass spectrometry detected physical interaction between cucurbitacin B and glutathione in a cell-free system.

UV spectroscopy and FTICR mass spectrometry detected physical interaction between cucurbitacin B and N-acetylcysteine in a cell-free system.

Adding cucurbitacin B rapidly lowered measured protein-thiol levels in human NSCLC cells.

Cucurbitacin B exposure lowered the GSH/GSSG ratio in the human NSCLC experiments.

Pretreating human NSCLC cells with the glutathione-synthesis inhibitor BSO increased cucurbitacin B cytotoxicity.

Adding N-acetylcysteine attenuated the reported cucurbitacin B cellular effects in the human NSCLC study.

Cucurbitacin I reduced heregulin-evoked Rac1 activation in human breast-cancer cells.

Cucurbitacin I activated RhoA/ROCK signaling; disrupting this pathway prevented the observed Rac1 inhibition.

Silencing STAT3 or JAK2 did not reproduce cucurbitacin I-mediated Rac1 inhibition in the tested human breast-cancer cells.

Mito-TEMPO and NAC prevented tested cucurbitacin I effects on Rac1 activation, supporting mitochondrial ROS involvement alongside the thiol-interception caveat for NAC.

Cucurbitacin B lowered TNF receptor 1 expression in human A549 cells without reducing the measured TRADD, RIPK1 and TRAF2 adaptor proteins.

Adding a TNF-alpha-converting-enzyme inhibitor suppressed cucurbitacin B-associated TNFR1 down-regulation in human A549 cells.

Cucurbitacin B reduced TNF-alpha-induced RelA nuclear translocation and I-kappa-B-alpha phosphorylation in human A549 cells.

Cucurbitacin B decreased ICAM1 expression induced by TNF-alpha or IL-1-alpha in human A549 cells.

Adding glutathione attenuated cucurbitacin B inhibition of TNF-alpha-induced ICAM1 expression; L-cysteine had a smaller effect than the other tested thiols.

Adding N-acetylcysteine attenuated cucurbitacin B inhibition of TNF-alpha-induced ICAM1 expression; L-cysteine had a smaller effect than the other tested thiols.

Adding L-cysteine attenuated cucurbitacin B inhibition of TNF-alpha-induced ICAM1 expression; L-cysteine had a smaller effect than the other tested thiols.

Cucurbitacin B exposure decreased GPX4 protein expression in the human nasopharyngeal-cancer experiments.

In human H358 and A549 cells, deferoxamine, ferrostatin-1 and liproxstatin-1 reversed cucurbitacin B growth inhibition, supporting a ferroptotic component.

Cucurbitacin B increased lipid ROS, malondialdehyde and measured ferrous iron while lowering glutathione in H358 and A549 experiments.

Docking and cellular thermal-shift experiments supported STAT3 target engagement by cucurbitacin B, alongside reduced STAT3 phosphorylation.

STAT3 overexpression reversed tested cucurbitacin B-associated lipid ROS and iron changes, whereas STAT3 silencing enhanced them.

Docking and CETSA supported an interaction between cucurbitacin B and TLR4 in the NSCLC study.

TLR4 silencing reduced cucurbitacin B-induced pyroptosis and associated mitochondrial ROS and calcium signals in human NSCLC cells.

Cucurbitacin B exposure was associated with the TLR4/mitochondrial-ROS/NLRP3 route and gasdermin D cleavage in the NSCLC pyroptosis experiments.

Cucurbitacin D at 0.1–1 micromolar reduced glucose uptake and lactate output in human PC3 and DU145 experiments.

Cucurbitacin D decreased GLUT1 expression in the prostate-cancer study; miR-132-associated changes were also reported.

Molecular docking proposed cucurbitacin D binding to GLUT1.

Cucurbitacin D interfered with EGF–EGFR binding in a solid-phase binding assay and reduced EGFR phosphorylation in the NSCLC study.

Cucurbitacin D enhanced LPS-associated IL-1-beta production and caspase-1-dependent inflammasome activation; the study reported NLRP3–ASC interaction and an ERK-dependent transcription component.

Male Wistar rats receiving oral cucurbitacin B at 2–4 mg/kg versus intravenous 0.1 mg/kg had estimated oral bioavailability of about 10%, with oral peak around 30 minutes.

The rat study estimated intravenous distribution volume near 51.65 L/kg ; lung and spleen tissue/plasma ratios were about 60 at 1 hour and about 240 at 2 hours, while liver, stomach and small intestine ratios were only 4–14 at 1 hour.

Rat cucurbitacin B metabolism profiling detected a cysteine conjugate among phase-II products; 13 metabolites were identified and seven confirmed in the overall study.

Rat cucurbitacin B metabolism profiling identified glutathione conjugation among the phase-II routes.

The cucurbitacin B cysteine conjugate retained antiproliferative activity in tested HepG2, MCF7 and PANC1 cells.

At equal oral formulation doses, nanosuspension increased measured peak concentration and exposure area for cucurbitacins B, D and E in rats.

In 353 French poison-center cases involving non-edible squash, 204 were symptomatic, predominantly with gastrointestinal effects; the series included dehydration or hypotension and recorded no severe cases or deaths.

Glutamate-cysteine ligase joins glutamate and cysteine to form gamma-glutamylcysteine in the first glutathione-synthesis step.

Purified PHGPX (GPX4) with glutathione reduced phospholipid hydroperoxides within photooxidized human erythrocyte ghost membranes to alcohol products without prior phospholipase cleavage.

At a physiological vitamin E-to-phospholipid ratio, inhibition of iron-dependent lipid peroxidation in rat liver microsomes and dispersed microsomal lipids was observed only when PHGPX (GPX4) and glutathione were also present.

Maternal dietary supplementation with 500 IU/kg DL-alpha-tocopheryl acetate through gestation and nursing allowed Alb-Cre;Gpx4fl/fl pups to survive to weaning, whereas liver-specific Gpx4-null pups on standard chow died within 48 hours after birth.

After six weeks on vitamin E-enriched diets, switching liver-specific Gpx4-null mice to vitamin E-deficient diet caused extensive hepatocellular necrosis and loss of the prior survival rescue; control genotypes survived the monitored 78 days after withdrawal.

Another defense changes how vulnerable cells are to GPX4 loss.

Disrupted selenium uptake hindered GPX4 production in these cancer cells.

Replacing selenium with sulfur retains some function but weakens peroxide resistance.

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