{"id":"eb32a3b5-1103-5b10-86cc-2bdd933c2fee","stable_key":"e0ea2d6a-7429-5e9f-b774-41e5e3288da3:e-sig-cehc-a549-pge2","predicate":"reduces-production-of","statement":"Gamma-CEHC suppressed cytokine-stimulated PGE2 in A549 cells, with an apparent IC50 near 30 µM. It also inhibited PGE2 after only 1 h exposure of COX-2-preinduced cells before arachidonic acid addition.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"c897596d-f072-57c9-9c52-c0509e398c2a","mechanism_event_label":"A breakdown product of gamma-tocopherol reduced prostaglandin production in a human lung cell model, including after brief exposure.","subject":{"id":"9a29222e-814f-572f-892d-1016a534506f","slug":"gamma-cehc","display_name":"Gamma-carboxyethyl hydroxychromanol","entity_type_key":"small_molecule"},"object":{"id":"5733d7d1-6259-588f-a4a9-4d0dc0133735","slug":"prostaglandin-e2","display_name":"Prostaglandin E2","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"c897596d-f072-57c9-9c52-c0509e398c2a","stable_key":"e0ea2d6a-7429-5e9f-b774-41e5e3288da3:e-sig-cehc-a549-pge2-event","event_type":"biochemical_relationship","label":"A breakdown product of gamma-tocopherol reduced prostaglandin production in a human lung cell model, including after brief exposure.","description":"Gamma-CEHC suppressed cytokine-stimulated PGE2 in A549 cells, with an apparent IC50 near 30 µM. It also inhibited PGE2 after only 1 h exposure of COX-2-preinduced cells before arachidonic acid addition.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"39f9446f-52a6-502d-b507-91137726f82c","slug":"arachidonic-acid","display_name":"AA","entity_type_key":"small_molecule"},"role":"added assay substrate","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"c8a31ed4-f2ca-5d43-8352-e9935129a785","slug":"ptgs2","display_name":"Cyclooxygenase-2 (PTGS2)","entity_type_key":"protein"},"role":"preinduced enzyme","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"9a29222e-814f-572f-892d-1016a534506f","slug":"gamma-cehc","display_name":"Gamma-carboxyethyl hydroxychromanol","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"5733d7d1-6259-588f-a4a9-4d0dc0133735","slug":"prostaglandin-e2","display_name":"Prostaglandin E2","entity_type_key":"small_molecule"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"false","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"A549 culture and preinduced cellular COX assay","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"IL-1β 10 ng/mL for 24 h; postinduction gamma-CEHC 1 h, then 5 or 15 µM arachidonic acid for 10 min at 37°C.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Cancer-derived culture, not treatment evidence. Intact-cell IC50 and purified COX inhibition are distinct measurements; increasing substrate weakened inhibition.","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":"A breakdown product of gamma-tocopherol reduced prostaglandin production in a human lung cell model, including after brief exposure.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[jiang2000] gamma-tocopherol and its major metabolite, in contrast to alpha-tocopherol, inhibit cyclooxygenase activity in macrophages and epithelial cells. (2000). https://pubmed.ncbi.nlm.nih.gov/11005841/ DOI: 10.1073/pnas.200357097","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Lung epithelial carcinoma cell line","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"38ddc3e5-c64e-54fd-b57d-7acaf4d11c87","evidence_kind":"source_excerpt","locator":"Lines 842-853","start_line":842,"end_line":853,"excerpt":"### e-sig-cehc-a549-pge2\nGamma-CEHC suppressed cytokine-stimulated PGE2 in A549 cells, with an apparent IC50 near 30 µM. It also inhibited PGE2 after only 1 h exposure of COX-2-preinduced cells before arachidonic acid addition.\nCondition category: normal\nnutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: A breakdown product of gamma-tocopherol reduced prostaglandin production in a human lung cell model, including after brief exposure.\norganism: Homo sapiens\ntissue_or_cell_type: Lung epithelial carcinoma cell line\nexperimental_model: A549 culture and preinduced cellular COX assay\nlimitations: Cancer-derived culture, not treatment evidence. Intact-cell IC50 and purified COX inhibition are distinct measurements; increasing substrate weakened inhibition.\nexposure: IL-1β 10 ng/mL for 24 h; postinduction gamma-CEHC 1 h, then 5 or 15 µM arachidonic acid for 10 min at 37°C.\ncross_nutrient: false\n[jiang2000] gamma-tocopherol and its major metabolite, in contrast to alpha-tocopherol, inhibit cyclooxygenase activity in macrophages and epithelial cells. (2000). https://pubmed.ncbi.nlm.nih.gov/11005841/ DOI: 10.1073/pnas.200357097","model_system":"A549 culture and preinduced cellular COX assay","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [jiang2000] gamma-tocopherol and its major metabolite, in contrast to alpha-tocopherol, inhibit cyclooxygenase activity in macrophages and epithelial cells. (2000). https://pubmed.ncbi.nlm.nih.gov/11005841/ DOI: 10.1073/pnas.200357097","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"3ac41dba-4727-5116-a556-ac3bbb0dc41c","stable_key":"import-e0ea2d6a-7429-5e9f-b774-41e5e3288da3","title":"Vitamin E: transport, membrane protection and nutrient 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. Not publisher full text.","file_path":"","sha256":"a90b6565e092c6a2da07f74cf758792c2cf63b40746260c8ff12bd64322c36f4","revision_id":"956793d1-23e4-5397-9291-25c1732a8e02","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}