{"id":"422e7aad-6fd4-59c1-a71c-ac96b6425d8a","stable_key":"182336c6-ed36-5ec6-8a09-25c31096262e:dim-nsclc-nfe2l2","predicate":"reduces_expression_in_nsclc","statement":"DIM treatment reduced NRF2 in the tested lung-cancer models.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"3bdd952a-e2b4-5667-9452-e98aed164054","mechanism_event_label":"A particular tumor context showed suppression of this defense/signaling component.","subject":{"id":"6009bdd4-f1b5-5867-b5c3-cdf7c9645cd0","slug":"dim","display_name":"3,3'-Diindolylmethane / DIM","entity_type_key":"small_molecule"},"object":{"id":"dc472dd3-d383-567a-ab37-a9ec4e112df4","slug":"nfe2l2","display_name":"Human Nrf2 / NFE2L2","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"3bdd952a-e2b4-5667-9452-e98aed164054","stable_key":"182336c6-ed36-5ec6-8a09-25c31096262e:dim-nsclc-nfe2l2-event","event_type":"biochemical_relationship","label":"A particular tumor context showed suppression of this defense/signaling component.","description":"DIM treatment reduced NRF2 in the tested lung-cancer models.","status":"provisional","compartment":null,"participants":[{"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":0,"notes":""},{"entity":{"id":"dc472dd3-d383-567a-ab37-a9ec4e112df4","slug":"nfe2l2","display_name":"Human Nrf2 / NFE2L2","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"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":"A particular tumor context showed suppression of this defense/signaling component.","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":"8f9330d2-3d6c-5877-b26e-feadd3ba44c3","evidence_kind":"source_excerpt","locator":"Lines 1299-1310","start_line":1299,"end_line":1310,"excerpt":"### dim-nsclc-nfe2l2\nDIM treatment reduced NRF2 in the tested lung-cancer models.\nCondition category: normal\nnutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: A particular tumor context showed suppression of this defense/signaling component.\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. (2025). https://pubmed.ncbi.nlm.nih.gov/40100489/ DOI: 10.1007/s12672-025-02096-z","model_system":"Cell perturbation and xenograft experiments","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [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","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"b6d70682-97f9-5893-a03c-f9f88836033c","stable_key":"import-182336c6-ed36-5ec6-8a09-25c31096262e","title":"Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. 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