{"id":"a4143c36-1940-5744-8213-8a07209a07c8","stable_key":"182336c6-ed36-5ec6-8a09-25c31096262e:dim-nsclc-ferroptosis","predicate":"induces_in_nsclc","statement":"DIM induced ferroptosis that could be reversed by ferrostatin-1, NAC or the tested AHR antagonist; NRF2 overexpression also reversed it.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"efd051a6-fad5-5fd3-86d8-9167ec990499","mechanism_event_label":"Perturbation controls helped connect the response to specific defenses.","subject":{"id":"6009bdd4-f1b5-5867-b5c3-cdf7c9645cd0","slug":"dim","display_name":"3,3'-Diindolylmethane / DIM","entity_type_key":"small_molecule"},"object":{"id":"85ca0bb8-8a67-59fe-8334-e0f6617380b7","slug":"ferroptosis","display_name":"Ferroptosis","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"efd051a6-fad5-5fd3-86d8-9167ec990499","stable_key":"182336c6-ed36-5ec6-8a09-25c31096262e:dim-nsclc-ferroptosis-event","event_type":"biochemical_relationship","label":"Perturbation controls helped connect the response to specific defenses.","description":"DIM induced ferroptosis that could be reversed by ferrostatin-1, NAC or the tested AHR antagonist; NRF2 overexpression also reversed it.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"b5fa7a22-e5a7-58d9-9e39-91a611aa431e","slug":"n-acetylcysteine","display_name":"N-Acetyl-L-cysteine","entity_type_key":"small_molecule"},"role":"rescue_control","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"dc472dd3-d383-567a-ab37-a9ec4e112df4","slug":"nfe2l2","display_name":"Human Nrf2 / NFE2L2","entity_type_key":"protein"},"role":"overexpression_rescue","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"e9bb13ee-f238-51e6-9101-78ddfd11465c","slug":"gpx4","display_name":"GPX4","entity_type_key":"protein"},"role":"downstream_defense","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"6009bdd4-f1b5-5867-b5c3-cdf7c9645cd0","slug":"dim","display_name":"3,3'-Diindolylmethane / DIM","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"85ca0bb8-8a67-59fe-8334-e0f6617380b7","slug":"ferroptosis","display_name":"Ferroptosis","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/dim-research/40100489.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"99bc986298e026c4bd40745004936bab65af37a931084f75634b89505f5b95d0\", \"start_char\": 0, \"end_char\": 1722, \"text_sha256\": \"99bc986298e026c4bd40745004936bab65af37a931084f75634b89505f5b95d0\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Cell perturbation and xenograft experiments","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"DIM; NRF2 overexpression and pharmacological rescue controls","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Preclinical cancer context. Reduced defense here differs from Nrf2 induction in fibroblasts; neither result proves a universal antioxidant or prooxidant effect in people.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"dim","display_name":"3,3'-Diindolylmethane / DIM","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Human non-small-cell lung-cancer cells and mouse xenografts","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Perturbation controls helped connect the response to specific defenses.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[dim-p40100489] 3,3'-diindolylmethane induces ferroptosis and inhibits proliferation in non-small-cell lung cancer through the AHR/NRF2/GPX4 axis. (2025). https://pubmed.ncbi.nlm.nih.gov/40100489/ DOI: 10.1007/s12672-025-02096-z","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Ferroptosis and AHR/NRF2/GPX4","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"20686904-6850-520d-923f-92861f1a9740","evidence_kind":"source_excerpt","locator":"Lines 1351-1362","start_line":1351,"end_line":1362,"excerpt":"### dim-nsclc-ferroptosis\nDIM induced ferroptosis that could be reversed by ferrostatin-1, NAC or the tested AHR antagonist; NRF2 overexpression also reversed it.\nCondition category: normal\nnutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Perturbation controls helped connect the response to specific defenses.\norganism: Human non-small-cell lung-cancer cells and mouse xenografts\ntissue_or_cell_type: Ferroptosis and AHR/NRF2/GPX4\nexperimental_model: Cell perturbation and xenograft experiments\nlimitations: Preclinical cancer context. Reduced defense here differs from Nrf2 induction in fibroblasts; neither result proves a universal antioxidant or prooxidant effect in people.\nexposure: DIM; NRF2 overexpression and pharmacological rescue controls\nevidence_span: {\"source_cache\": \"artifacts/dim-research/40100489.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"99bc986298e026c4bd40745004936bab65af37a931084f75634b89505f5b95d0\", \"start_char\": 0, \"end_char\": 1722, \"text_sha256\": \"99bc986298e026c4bd40745004936bab65af37a931084f75634b89505f5b95d0\"}\n[dim-p40100489] 3,3'-diindolylmethane induces ferroptosis and inhibits proliferation in non-small-cell lung cancer through the AHR/NRF2/GPX4 axis. 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