{"id":"ba2b8c20-0d2b-56f3-928d-1bafe57f1da9","stable_key":"3d41d18a-e13a-59a0-a081-55bfcdd43e55:ceylon-nrf2-ubiquitin","predicate":"decreases","statement":"Cinnamaldehyde blocked NRF2 ubiquitination in HCT116 cells through a KEAP1-C151-dependent mechanism.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"03f885b9-af12-542d-8518-d01d3fbe1e86","mechanism_event_label":"The cell marked less NRF2 for disposal.","subject":{"id":"2dc093c6-9373-5b24-a17b-a6b21b5a0432","slug":"trans-cinnamaldehyde","display_name":"trans-Cinnamaldehyde / cinnamal","entity_type_key":"small_molecule"},"object":{"id":"0f495f1a-3314-54bd-8960-b35c6f5d7a69","slug":"nrf2-ubiquitination","display_name":"KEAP1-dependent Nrf2 ubiquitination","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"03f885b9-af12-542d-8518-d01d3fbe1e86","stable_key":"3d41d18a-e13a-59a0-a081-55bfcdd43e55:ceylon-nrf2-ubiquitin-event","event_type":"biochemical_relationship","label":"The cell marked less NRF2 for disposal.","description":"Cinnamaldehyde blocked NRF2 ubiquitination in HCT116 cells through a KEAP1-C151-dependent mechanism.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"dc472dd3-d383-567a-ab37-a9ec4e112df4","slug":"nfe2l2","display_name":"Human Nrf2 / NFE2L2","entity_type_key":"protein"},"role":"regulated_protein","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"4fdd282e-0fc0-5369-88e6-c192d063c7b7","slug":"cinnamaldehyde-keap1-c151-construct","display_name":"KEAP1 C151-sensitive construct in the 2015 cinnamaldehyde study; construct species unresolved from abstract","entity_type_key":"protein_family"},"role":"mechanistic_construct","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"2dc093c6-9373-5b24-a17b-a6b21b5a0432","slug":"trans-cinnamaldehyde","display_name":"trans-Cinnamaldehyde / cinnamal","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"0f495f1a-3314-54bd-8960-b35c6f5d7a69","slug":"nrf2-ubiquitination","display_name":"KEAP1-dependent Nrf2 ubiquitination","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/ceylon-research/25712056.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"8ad37b0dca440e7fa609a46cf02377c2979d2be8e09291a370efb963ff3c9cfd\", \"start_char\": 0, \"end_char\": 1920, \"text_sha256\": \"8ad37b0dca440e7fa609a46cf02377c2979d2be8e09291a370efb963ff3c9cfd\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"HCT116 mechanism and AOM/DSS knockout-mouse experiment","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Purified cinnamaldehyde cell exposure and dietary supplementation in mice","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"No human cancer-prevention outcome; the abstract identifies C151 dependence but does not resolve the transfected KEAP1 construct species.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Ceylon cinnamon research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"ceylon","display_name":"Ceylon cinnamon / Cinnamomum verum bark preparations","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Human HCT116 cells; KEAP1 construct species unresolved","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The cell marked less NRF2 for disposal.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[ceylon-p25712056] Nrf2-dependent suppression of azoxymethane/dextran sulfate sodium-induced colon carcinogenesis by the cinnamon-derived dietary factor cinnamaldehyde. (2015). https://pubmed.ncbi.nlm.nih.gov/25712056/ DOI: 10.1158/1940-6207.capr-14-0359","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Colon epithelial cancer cells and experimental inflammatory colon tumors","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"2f0ca32e-52bf-54a9-be26-4eeaa7b64ffd","evidence_kind":"source_excerpt","locator":"Lines 597-608","start_line":597,"end_line":608,"excerpt":"### ceylon-nrf2-ubiquitin\nCinnamaldehyde blocked NRF2 ubiquitination in HCT116 cells through a KEAP1-C151-dependent mechanism.\nCondition category: normal\nnutrient_topic: Ceylon cinnamon research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The cell marked less NRF2 for disposal.\norganism: Human HCT116 cells; KEAP1 construct species unresolved\ntissue_or_cell_type: Colon epithelial cancer cells and experimental inflammatory colon tumors\nexperimental_model: HCT116 mechanism and AOM/DSS knockout-mouse experiment\nlimitations: No human cancer-prevention outcome; the abstract identifies C151 dependence but does not resolve the transfected KEAP1 construct species.\nexposure: Purified cinnamaldehyde cell exposure and dietary supplementation in mice\nevidence_span: {\"source_cache\": \"artifacts/ceylon-research/25712056.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"8ad37b0dca440e7fa609a46cf02377c2979d2be8e09291a370efb963ff3c9cfd\", \"start_char\": 0, \"end_char\": 1920, \"text_sha256\": \"8ad37b0dca440e7fa609a46cf02377c2979d2be8e09291a370efb963ff3c9cfd\"}\n[ceylon-p25712056] Nrf2-dependent suppression of azoxymethane/dextran sulfate sodium-induced colon carcinogenesis by the cinnamon-derived dietary factor cinnamaldehyde. 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