{"id":"3b371046-105d-5036-afce-82b8b3abe064","stable_key":"e3f6ce02-0bd7-5103-acc1-68503ab6751b:hcc-p300-block","predicate":"decreases_in_recorded_comparison","statement":"p300/CBP inhibition blocked the ALCAR-associated proliferation rescue in lipid-depleted ACLY/ACSS2-null HCC cells.","claim_class":"observational","status":"source_recorded","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"65f13319-bb08-5eb1-adca-0aaea384e837","mechanism_event_label":"p300/CBP inhibition blocked the ALCAR-associated proliferation rescue in lipid-depleted ACLY/ACSS2-null HCC cells.","subject":{"id":"7ab39670-ef17-5d3c-ac60-4f7abd5741c0","slug":"a-485","display_name":"A-485 p300/CBP catalytic inhibitor","entity_type_key":"drug"},"object":{"id":"11c8b10f-51b9-549b-a2ce-fd77e9717686","slug":"mouse-hcc-alcar-growth","display_name":"Mouse HCC proliferation rescued by acetylcarnitine","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"65f13319-bb08-5eb1-adca-0aaea384e837","stable_key":"e3f6ce02-0bd7-5103-acc1-68503ab6751b:hcc-p300-block-event","event_type":"experimental_observation","label":"p300/CBP inhibition blocked the ALCAR-associated proliferation rescue in lipid-depleted ACLY/ACSS2-null HCC cells.","description":"### hcc-p300-block\n\np300/CBP inhibition blocked the ALCAR-associated proliferation rescue in lipid-depleted ACLY/ACSS2-null HCC cells.\nA-485 suppressed H3K27 acetylation but not H3K23 acetylation in this comparison. ACC inhibition did not block the growth rescue, separating acetylation from obligatory de novo lipogenesis.\nModel and exposure: Mouse HCC cells; A-485; Fig. 6G–H.\nLimitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.\nReference: Acetylcarnitine shuttling links mitochondrial metabolism to histone acetylation and lipogenesis. | 2023 | https://pubmed.ncbi.nlm.nih.gov/37134161/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC10156126/ | https://doi.org/10.1126/sciadv.adf0115 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"7ab39670-ef17-5d3c-ac60-4f7abd5741c0","slug":"a-485","display_name":"A-485 p300/CBP catalytic inhibitor","entity_type_key":"drug"},"role":"tested factor","stoichiometry":null,"state_label":"A-485 plus ALCAR in lipid-depleted double-knockout cells","sequence_order":0,"notes":""},{"entity":{"id":"11c8b10f-51b9-549b-a2ce-fd77e9717686","slug":"mouse-hcc-alcar-growth","display_name":"Mouse HCC proliferation rescued by acetylcarnitine","entity_type_key":"cellular_process"},"role":"measured outcome","stoichiometry":null,"state_label":"decrease","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_condition","value_text":"present","comparator":"ALCAR-treated double-knockout cells without A-485","unit":null,"notes":"Condition belongs to the full experimental contrast; do not separate a joint intervention.","entity":{"slug":"a-485","display_name":"A-485 p300/CBP catalytic inhibitor","entity_type_key":"drug"}},{"dimension":"experimental_condition","value_text":"present","comparator":"ALCAR-treated double-knockout cells without A-485","unit":null,"notes":"Condition belongs to the full experimental contrast; do not separate a joint intervention.","entity":{"slug":"acetylcarnitine","display_name":"Acetyl-L-carnitine","entity_type_key":"small_molecule"}},{"dimension":"experimental_condition","value_text":"deleted","comparator":"ALCAR-treated double-knockout cells without A-485","unit":null,"notes":"Condition belongs to the full experimental contrast; do not separate a joint intervention.","entity":{"slug":"mouse-acly","display_name":"Mouse ATP-citrate lyase / Acly","entity_type_key":"protein"}},{"dimension":"experimental_condition","value_text":"deleted","comparator":"ALCAR-treated double-knockout cells without A-485","unit":null,"notes":"Condition belongs to the full experimental contrast; do not separate a joint intervention.","entity":{"slug":"mouse-acss2","display_name":"Mouse acyl-CoA synthetase short-chain family member 2 / Acss2","entity_type_key":"protein"}},{"dimension":"experimental_contrast","value_text":"{\"intervention\": \"A-485 plus ALCAR in lipid-depleted double-knockout cells\", \"comparator\": \"ALCAR-treated double-knockout cells without A-485\", \"endpoint\": \"p300/CBP inhibition blocked the ALCAR-associated proliferation rescue in lipid-depleted ACLY/ACSS2-null HCC cells.\", \"effect_direction\": \"decrease\", \"combination\": \"joint\", \"conditions\": [{\"entity_slug\": \"a-485\", \"state\": \"present\"}, {\"entity_slug\": \"acetylcarnitine\", \"state\": \"present\"}, {\"entity_slug\": \"mouse-acly\", \"state\": \"deleted\"}, {\"entity_slug\": \"mouse-acss2\", \"state\": \"deleted\"}]}","comparator":null,"unit":null,"notes":"Explicit extracted experimental comparison; source-derived draft.","entity":null},{"dimension":"experimental_model","value_text":"Mouse HCC cells; A-485; Fig. 6G–H.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"interpretation_status","value_text":"Source-derived curation with stated access limits; ungraded, not independent replication.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation.","comparator":null,"unit":null,"notes":"","entity":{"slug":"acetylcarnitine","display_name":"Acetyl-L-carnitine","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"p300/CBP inhibition blocked the ALCAR-associated proliferation rescue in lipid-depleted ACLY/ACSS2-null HCC cells.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Acetylcarnitine shuttling links mitochondrial metabolism to histone acetylation and lipogenesis. | https://pubmed.ncbi.nlm.nih.gov/37134161/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC10156126/ | https://doi.org/10.1126/sciadv.adf0115","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"source_locator","value_text":"Reviewed reference hcc-p300-block; A-485 suppressed H3K27 acetylation but not H3K23 acetylation in this comparison. ACC inhibition did not block the growth rescue, separating acetylation from obligatory de novo lipogenesis.","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"5dd69ed0-4f84-5dc6-baec-189f0346780d","evidence_kind":"source_excerpt","locator":"Lines 268-274","start_line":268,"end_line":274,"excerpt":"### hcc-p300-block\n\np300/CBP inhibition blocked the ALCAR-associated proliferation rescue in lipid-depleted ACLY/ACSS2-null HCC cells.\nA-485 suppressed H3K27 acetylation but not H3K23 acetylation in this comparison. ACC inhibition did not block the growth rescue, separating acetylation from obligatory de novo lipogenesis.\nModel and exposure: Mouse HCC cells; A-485; Fig. 6G–H.\nLimitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.\nReference: Acetylcarnitine shuttling links mitochondrial metabolism to histone acetylation and lipogenesis. | 2023 | https://pubmed.ncbi.nlm.nih.gov/37134161/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC10156126/ | https://doi.org/10.1126/sciadv.adf0115 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.","model_system":"Mouse HCC cells; A-485; Fig. 6G–H.","directness":"reported_statement","verification_status":"source_recorded","notes":"Original paraphrase in the retained reviewed reference, not a verbatim primary-paper quotation. Access level is explicit.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"2588f904-245a-597a-8a12-65118013fb90","stable_key":"import-e3f6ce02-0bd7-5103-acc1-68503ab6751b","title":"Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026)","document_type":"imported_text","citation_label":"AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed.","file_path":"","sha256":"84cc82d6fbb0fd5d73c4ce779e9f88e7f0184ba2d29b18ad0f153815380f2975","revision_id":"dac7a950-dbe5-5c7a-9c70-2ea711d5c71a","review_status":"source_recorded","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}