{"id":"b5c798f5-575e-5c9b-a8d1-65f590332edd","stable_key":"e0ea2d6a-7429-5e9f-b774-41e5e3288da3:ver-alpha-t3-cellular-oxidation","predicate":"inhibits","statement":"In HT-1080 cells challenged with the GPX4 inhibitor RSL3, alpha-tocotrienol suppressed the oxidized C11-BODIPY signal at lower tested concentrations than alpha-tocopherol.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"dd4cfff8-a9e2-523e-9e64-04db403d8eee","mechanism_event_label":"Alpha-tocotrienol more effectively limited the lipid-oxidation reporter in this cancer-cell assay.","subject":{"id":"45597684-ead7-5ebe-975a-ac3bc714e22c","slug":"alpha-tocotrienol","display_name":"Alpha-tocotrienol","entity_type_key":"small_molecule"},"object":{"id":"f00627d2-4857-5c63-81af-71cde3768d38","slug":"lipid-peroxidation","display_name":"Lipid peroxidation","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"dd4cfff8-a9e2-523e-9e64-04db403d8eee","stable_key":"e0ea2d6a-7429-5e9f-b774-41e5e3288da3:ver-alpha-t3-cellular-oxidation-event","event_type":"biochemical_relationship","label":"Alpha-tocotrienol more effectively limited the lipid-oxidation reporter in this cancer-cell assay.","description":"In HT-1080 cells challenged with the GPX4 inhibitor RSL3, alpha-tocotrienol suppressed the oxidized C11-BODIPY signal at lower tested concentrations than alpha-tocopherol.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"40a6525a-76b8-576e-b73d-1e11aecf5f8d","slug":"alpha-tocopherol","display_name":"Alpha-tocopherol","entity_type_key":"small_molecule"},"role":"comparator","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"e9bb13ee-f238-51e6-9101-78ddfd11465c","slug":"gpx4","display_name":"GPX4","entity_type_key":"protein"},"role":"pharmacologically inhibited enzyme","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"45597684-ead7-5ebe-975a-ac3bc714e22c","slug":"alpha-tocotrienol","display_name":"Alpha-tocotrienol","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"f00627d2-4857-5c63-81af-71cde3768d38","slug":"lipid-peroxidation","display_name":"Lipid peroxidation","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"true","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_location","value_text":"Figure 4B","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"RSL3 challenge and flow-cytometric C11-BODIPY assay","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"E forms at 1 and 30 µM for 1 h before 0.5 µM RSL3 for 2 h.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Potency in cell assays does not establish nutritional equivalence or human efficacy; the study also detected toxicity at higher concentrations, with tocotrienols toxic at lower concentrations than tocopherols. Probe oxidation is not a chemically resolved inventory of endogenous phospholipid products.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Vitamin E research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"vitamin-e","display_name":"Vitamin E","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Alpha-tocotrienol more effectively limited the lipid-oxidation reporter in this cancer-cell assay.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[ver-yang2026] Tocotrienols exhibit superior ferroptosis inhibition over tocopherols. (2026). https://pubmed.ncbi.nlm.nih.gov/41501350/ DOI: 10.1038/s41598-025-34673-1","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"HT-1080 fibrosarcoma cells","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"207577aa-c5bc-5f9e-a0b8-49490c9427d4","evidence_kind":"source_excerpt","locator":"Lines 802-814","start_line":802,"end_line":814,"excerpt":"### ver-alpha-t3-cellular-oxidation\nIn HT-1080 cells challenged with the GPX4 inhibitor RSL3, alpha-tocotrienol suppressed the oxidized C11-BODIPY signal at lower tested concentrations than alpha-tocopherol.\nCondition category: normal\nnutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Alpha-tocotrienol more effectively limited the lipid-oxidation reporter in this cancer-cell assay.\norganism: Homo sapiens\ntissue_or_cell_type: HT-1080 fibrosarcoma cells\nexperimental_model: RSL3 challenge and flow-cytometric C11-BODIPY assay\nlimitations: Potency in cell assays does not establish nutritional equivalence or human efficacy; the study also detected toxicity at higher concentrations, with tocotrienols toxic at lower concentrations than tocopherols. Probe oxidation is not a chemically resolved inventory of endogenous phospholipid products.\nexposure: E forms at 1 and 30 µM for 1 h before 0.5 µM RSL3 for 2 h.\ncross_nutrient: true\nevidence_location: Figure 4B\n[ver-yang2026] Tocotrienols exhibit superior ferroptosis inhibition over tocopherols. (2026). https://pubmed.ncbi.nlm.nih.gov/41501350/ DOI: 10.1038/s41598-025-34673-1","model_system":"RSL3 challenge and flow-cytometric C11-BODIPY assay","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [ver-yang2026] Tocotrienols exhibit superior ferroptosis inhibition over tocopherols. 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