{"id":"58539129-d12e-5d04-9975-c9cfd9abe7a5","stable_key":"cea4b417-bb71-5d5d-8fe1-4e175aca750c:graviola-annonacin-cell-cycle","predicate":"induces","statement":"Purified annonacin activated p21, increased Bax and caspase-3, and produced G1 arrest and cell death in cultured T24 bladder-cancer cells.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"ae0bb679-0c2d-50b3-8538-f4c57a680cb3","mechanism_event_label":"Purified annonacin activated p21, increased Bax and caspase-3, and produced G1 arrest and cell death in cultured T24 bladder-cancer cells.","subject":{"id":"46b657b6-1692-59cb-bccd-e94db35a2734","slug":"annonacin","display_name":"Annonacin","entity_type_key":"small_molecule"},"object":{"id":"f688ea15-d798-525e-8f79-997de53cc8ba","slug":"t24-cancer-cell-g1-arrest-and-apoptosis","display_name":"G1 arrest and apoptosis in T24 bladder-cancer cells","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"ae0bb679-0c2d-50b3-8538-f4c57a680cb3","stable_key":"cea4b417-bb71-5d5d-8fe1-4e175aca750c:graviola-annonacin-cell-cycle-event","event_type":"observed_relationship","label":"Purified annonacin activated p21, increased Bax and caspase-3, and produced G1 arrest and cell death in cultured T24 bladder-cancer cells.","description":"Purified annonacin activated p21, increased Bax and caspase-3, and produced G1 arrest and cell death in cultured T24 bladder-cancer cells.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"46b657b6-1692-59cb-bccd-e94db35a2734","slug":"annonacin","display_name":"Annonacin","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"f688ea15-d798-525e-8f79-997de53cc8ba","slug":"t24-cancer-cell-g1-arrest-and-apoptosis","display_name":"G1 arrest and apoptosis in T24 bladder-cancer cells","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"c2d61996-e216-593f-9621-71aba2448649","slug":"bax","display_name":"Human BAX","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"ed6af789-cd83-5830-8b51-8e1ff2d6871e","slug":"caspase3","display_name":"Caspase-3","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"dose","value_text":"Purified annonacin concentration-response","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"duration","value_text":"Up to 48 hours","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_access","value_text":"Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_scope","value_text":"literature_reviewed; model-specific source-derived curation","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human T24 bladder-cancer cells and other cancer lines","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Cancer-cell cytotoxicity does not establish tumor selectivity, human efficacy, or a safe graviola product.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Graviola (Annona muricata) chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings.","comparator":null,"unit":null,"notes":"","entity":{"slug":"graviola","display_name":"Graviola / Annona muricata","entity_type_key":"botanical"}},{"dimension":"organism","value_text":"Human T24 bladder-cancer cells and other cancer lines","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Purified annonacin activated p21, increased Bax and caspase-3, and produced G1 arrest and cell death in cultured T24 bladder-cancer cells.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Annonacin, a mono-tetrahydrofuran acetogenin, arrests cancer cells at the G1 phase and causes cytotoxicity in a Bax- and caspase-3-related pathway. (2003). https://pubmed.ncbi.nlm.nih.gov/12697268/ DOI: 10.1016/s0024-3205(03)00190-5","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"route","value_text":"In vitro","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue","value_text":"Cell cycle and apoptosis markers","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"c9b596ac-45c0-5984-9298-a7af1ac19b59","evidence_kind":"source_excerpt","locator":"Lines 99-108","start_line":99,"end_line":108,"excerpt":"## graviola-annonacin-cell-cycle\nPurified annonacin activated p21, increased Bax and caspase-3, and produced G1 arrest and cell death in cultured T24 bladder-cancer cells.\nModel/species: Human T24 bladder-cancer cells and other cancer lines\nTissue/system: Cell cycle and apoptosis markers\nExposure: Purified annonacin concentration-response\nRoute: In vitro\nDuration: Up to 48 hours\nLimits: Cancer-cell cytotoxicity does not establish tumor selectivity, human efficacy, or a safe graviola product.\nPrimary reference: Annonacin, a mono-tetrahydrofuran acetogenin, arrests cancer cells at the G1 phase and causes cytotoxicity in a Bax- and caspase-3-related pathway. (2003). https://pubmed.ncbi.nlm.nih.gov/12697268/ DOI: 10.1016/s0024-3205(03)00190-5\nAccess: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.","model_system":"Human T24 bladder-cancer cells and other cancer lines","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Exact original curation span with primary citation; not a publisher quotation.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"dde73deb-4328-5cc7-aa41-04b7d845f4fa","stable_key":"import-cea4b417-bb71-5d5d-8fe1-4e175aca750c","title":"Graviola (Annona muricata): mechanism of action and interactions (2026-09-20)","document_type":"imported_text","citation_label":"Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. 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