Component

RSL3-induced cell death in A375 cells

4 recorded relationships. Experimental role, claim status and evidence remain attached to each record.

Read recorded mechanisms Open recursive mind map

How nutrients influence it

Every nutrient with a recorded effect on this component, credited to the nutrient that acted rather than the chapter that recorded it. Open a nutrient to see the findings and the conditions they were measured under.

How nutrients reach it in more than one step

Chains of two or more recorded steps that end here, grouped by the nutrient they start from. Each step is a separate finding, so a chain is a route a mechanism could take, not proof that it does.

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What it does

Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.

Recorded relationships

What acts on it

  1. C2S APT2 re-expression did not reproduce wild-type restoration of RSL3 susceptibility in APT2-depleted A375 cells.

    Human A375 APT2 knockdown with HA-APT2 C2S re-expression → RSL3-induced cell death in A375 cells source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    experimental_model
    Human A375 melanoma cells with APT2 shRNA and lentiviral rescue constructs
    exposure
    HA-tagged rescue constructs; Figure 6j: 48-hour RSL3 challenge, n=3 independent experiments. Exact RSL3 concentrations follow the figure dose response and are not inferred here.
    limitations
    C2S affects APT2 palmitoylation/localization and is not identical to the S122A catalytic-site perturbation. Null comparisons do not prove equivalence. No sulforaphane or solasonine tested in this rescue experiment.
    organism
    Human
    primary_locator
    Figure 6i-j; Results: Inhibition of APT2 suppresses ferroptosis.
    primary_references
    https://doi.org/10.1038/s41467-025-56344-5
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    APT2, STAT3 and GPX4: opposing branches and assay qualification · lines 33–39

    Primary observations: 10.1038/s41467-025-56344-5 and 10.1002/ptr.70245; selected full-text review 2026-09-20. · supports · Human A375 melanoma cells with APT2 shRNA and lentiviral rescue constructs · source_derived_draft · unverified_draft

    C2S APT2 re-expression did not reproduce wild-type restoration of RSL3 susceptibility in APT2-depleted A375 cells. primary_references: https://doi.org/10.1038/s41467-025-56344-5 primary_locator: Figure 6i-j; Results: Inhibition of APT2 suppresses ferroptosis. organism: Human experimental_model: Human A375 melanoma cells with APT2 shRNA and lentiviral rescue constructs exposure: HA-tagged rescue constructs; Figure 6j: 48-hour RSL3 challenge, n=3 independent experiments. Exact RSL3 concentrations follow the figure dose response and are not inferred here. limitations: C2S affects APT2 palmitoylation/localization and is not identical to the S122A catalytic-site perturbation. Null comparisons do not prove equivalence. No sulforaphane or solasonine tested in this rescue experiment.
    Complete structured claim and evidence

  2. S122A APT2 re-expression did not reproduce wild-type restoration of RSL3 susceptibility in APT2-depleted A375 cells.

    Human A375 APT2 knockdown with HA-APT2 S122A re-expression → RSL3-induced cell death in A375 cells source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    experimental_model
    Human A375 melanoma cells with APT2 shRNA and lentiviral rescue constructs
    exposure
    HA-tagged rescue constructs; Figure 6j: 48-hour RSL3 challenge, n=3 independent experiments. Exact RSL3 concentrations follow the figure dose response and are not inferred here.
    limitations
    C2S affects APT2 palmitoylation/localization and is not identical to the S122A catalytic-site perturbation. Null comparisons do not prove equivalence. No sulforaphane or solasonine tested in this rescue experiment.
    organism
    Human
    primary_locator
    Figure 6i-j; Results: Inhibition of APT2 suppresses ferroptosis.
    primary_references
    https://doi.org/10.1038/s41467-025-56344-5
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    APT2, STAT3 and GPX4: opposing branches and assay qualification · lines 51–57

    Primary observations: 10.1038/s41467-025-56344-5 and 10.1002/ptr.70245; selected full-text review 2026-09-20. · supports · Human A375 melanoma cells with APT2 shRNA and lentiviral rescue constructs · source_derived_draft · unverified_draft

    S122A APT2 re-expression did not reproduce wild-type restoration of RSL3 susceptibility in APT2-depleted A375 cells. primary_references: https://doi.org/10.1038/s41467-025-56344-5 primary_locator: Figure 6i-j; Results: Inhibition of APT2 suppresses ferroptosis. organism: Human experimental_model: Human A375 melanoma cells with APT2 shRNA and lentiviral rescue constructs exposure: HA-tagged rescue constructs; Figure 6j: 48-hour RSL3 challenge, n=3 independent experiments. Exact RSL3 concentrations follow the figure dose response and are not inferred here. limitations: C2S affects APT2 palmitoylation/localization and is not identical to the S122A catalytic-site perturbation. Null comparisons do not prove equivalence. No sulforaphane or solasonine tested in this rescue experiment.
    Complete structured claim and evidence

  3. Wild-type APT2 re-expression restored RSL3 susceptibility in APT2-depleted A375 cells.

    Human A375 APT2 knockdown with HA-APT2 WT re-expression → RSL3-induced cell death in A375 cells source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    experimental_model
    Human A375 melanoma cells with APT2 shRNA and lentiviral rescue constructs
    exposure
    HA-tagged rescue constructs; Figure 6j: 48-hour RSL3 challenge, n=3 independent experiments. Exact RSL3 concentrations follow the figure dose response and are not inferred here.
    limitations
    C2S affects APT2 palmitoylation/localization and is not identical to the S122A catalytic-site perturbation. Null comparisons do not prove equivalence. No sulforaphane or solasonine tested in this rescue experiment.
    organism
    Human
    primary_locator
    Figure 6i-j; Results: Inhibition of APT2 suppresses ferroptosis.
    primary_references
    https://doi.org/10.1038/s41467-025-56344-5
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    APT2, STAT3 and GPX4: opposing branches and assay qualification · lines 15–21

    Primary observations: 10.1038/s41467-025-56344-5 and 10.1002/ptr.70245; selected full-text review 2026-09-20. · supports · Human A375 melanoma cells with APT2 shRNA and lentiviral rescue constructs · source_derived_draft · unverified_draft

    Wild-type APT2 re-expression restored RSL3 susceptibility in APT2-depleted A375 cells. primary_references: https://doi.org/10.1038/s41467-025-56344-5 primary_locator: Figure 6i-j; Results: Inhibition of APT2 suppresses ferroptosis. organism: Human experimental_model: Human A375 melanoma cells with APT2 shRNA and lentiviral rescue constructs exposure: HA-tagged rescue constructs; Figure 6j: 48-hour RSL3 challenge, n=3 independent experiments. Exact RSL3 concentrations follow the figure dose response and are not inferred here. limitations: C2S affects APT2 palmitoylation/localization and is not identical to the S122A catalytic-site perturbation. Null comparisons do not prove equivalence. No sulforaphane or solasonine tested in this rescue experiment.
    Complete structured claim and evidence

  4. APT2 knockdown reduced RSL3-induced cell death measured with SYTOX Green in A375 cells.

    Human APT2 knockdown in A375 → RSL3-induced cell death in A375 cells source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_cache
    artifacts/discovery-research/round6-sources/gpx4-primary-passages.json; SHA256 384aaae29ec0e6fe9814782b3e5d885753751fa1b2bbd103e30e8ffa113df5dc
    experimental_model
    Human A375 melanoma; lentiviral APT2 shRNA
    exposure
    4 micromolar RSL3 for 6 hours; SYTOX Green staining; three independent experiments.
    limitations
    These are separate experimental observations, not a demonstrated sulforaphane-GPX4-ZDHHC6 pathway. Sulforaphane-driven APT2 relocalization is not equivalent to genetic depletion or general catalytic inhibition. No dietary, clinical or selenium-repletion effect is inferred. Protein stability, palmitoylation and substrate output remain different measurements. This is a response to a GPX4 inhibitor in cancer cells. It does not establish an effect of sulforaphane or dietary selenium.
    organism
    Human experimental cells; construct species unresolved where stated for discussion-only nulls
    primary_locator
    Figure 6c,d
    primary_references
    https://doi.org/10.1038/s41467-025-56344-5
    source_access
    Selected primary Results and Figure 5/6 legends reviewed. No supplement or raw-data reanalysis.
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    APT2: sulforaphane engagement, GPX4 stability and ZDHHC6 turnover · lines 140–148

    Targeted primary-literature curation from recursive ZDHHC6 exploration, 2026-09-20. · supports · Human A375 melanoma; lentiviral APT2 shRNA · source_derived_draft · unverified_draft

    APT2 knockdown reduced RSL3-induced cell death measured with SYTOX Green in A375 cells. primary_references: https://doi.org/10.1038/s41467-025-56344-5 primary_locator: Figure 6c,d source_access: Selected primary Results and Figure 5/6 legends reviewed. No supplement or raw-data reanalysis. evidence_cache: artifacts/discovery-research/round6-sources/gpx4-primary-passages.json; SHA256 384aaae29ec0e6fe9814782b3e5d885753751fa1b2bbd103e30e8ffa113df5dc experimental_model: Human A375 melanoma; lentiviral APT2 shRNA organism: Human experimental cells; construct species unresolved where stated for discussion-only nulls exposure: 4 micromolar RSL3 for 6 hours; SYTOX Green staining; three independent experiments. limitations: These are separate experimental observations, not a demonstrated sulforaphane-GPX4-ZDHHC6 pathway. Sulforaphane-driven APT2 relocalization is not equivalent to genetic depletion or general catalytic inhibition. No dietary, clinical or selenium-repletion effect is inferred. Protein stability, palmitoylation and substrate output remain different measurements. This is a response to a GPX4 inhibitor in cancer cells. It does not establish an effect of sulforaphane or dietary selenium.
    Complete structured claim and evidence

In the sources

Preserved passages that mention this component, quoted exactly. Open one to read it in context.

    This is a research prototype built from draft material. It is not medical advice, and its statements still await verification against the original studies.

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