{"id":"7abad7cb-33be-5d01-9c17-06699bb91949","stable_key":"44eaeae5-557a-552b-8998-884f30462e2a:sulforaphane-histone-acetylation-down","predicate":"decreased","statement":"Sulforaphane decreased acetylated histone H3, H4 and tubulin markers in the cell comparisons despite reduced HDAC protein levels.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"43568d38-5266-55b1-b64d-3cdcdf4d2ae3","mechanism_event_label":"Less enzyme protein did not produce the expected increase in acetylation.","subject":{"id":"67e70215-70c4-546a-84b4-0819fac0b326","slug":"sulforaphane","display_name":"Sulforaphane / SFN, stereochemistry specified per study","entity_type_key":"small_molecule"},"object":{"id":"ec8d4882-1462-5107-8400-367298f439e1","slug":"histone-acetylation","display_name":"Core histone lysine acetylation","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"43568d38-5266-55b1-b64d-3cdcdf4d2ae3","stable_key":"44eaeae5-557a-552b-8998-884f30462e2a:sulforaphane-histone-acetylation-down-event","event_type":"biochemical_relationship","label":"Less enzyme protein did not produce the expected increase in acetylation.","description":"Sulforaphane decreased acetylated histone H3, H4 and tubulin markers in the cell comparisons despite reduced HDAC protein levels.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"67e70215-70c4-546a-84b4-0819fac0b326","slug":"sulforaphane","display_name":"Sulforaphane / SFN, stereochemistry specified per study","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"ec8d4882-1462-5107-8400-367298f439e1","slug":"histone-acetylation","display_name":"Core histone lysine acetylation","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/sulforaphane-research/25307283.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"cc736d6c2f2dc6c4026bdad0a5835d69ed094775076a2c1606f47020e6783331\", \"start_char\": 0, \"end_char\": 1504, \"text_sha256\": \"cc736d6c2f2dc6c4026bdad0a5835d69ed094775076a2c1606f47020e6783331\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Matched cell-type and time-course comparison","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Sulforaphane exposure; serum and time-course comparisons","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Activity assays, protein abundance and substrate acetylation are distinct endpoints; mechanism of their divergence was not established. Erratum PMID 27271518 adds an omitted funding acknowledgment without revising these results.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Sulforaphane research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"sulforaphane","display_name":"Sulforaphane / SFN, stereochemistry specified per study","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Human HaCaT keratinocytes and HCT116 colon cancer cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Less enzyme protein did not produce the expected increase in acetylation.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[sulforaphane-p25307283] The effect of sulforaphane on histone deacetylase activity in keratinocytes: Differences between in vitro and in vivo analyses. (2015). https://pubmed.ncbi.nlm.nih.gov/25307283/ DOI: 10.1002/mc.22224","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"HDAC activity, protein levels and target acetylation","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"5e0371d4-1923-5dac-af41-c0ea714b9d9f","evidence_kind":"source_excerpt","locator":"Lines 606-617","start_line":606,"end_line":617,"excerpt":"### sulforaphane-histone-acetylation-down\nSulforaphane decreased acetylated histone H3, H4 and tubulin markers in the cell comparisons despite reduced HDAC protein levels.\nCondition category: normal\nnutrient_topic: Sulforaphane research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Less enzyme protein did not produce the expected increase in acetylation.\norganism: Human HaCaT keratinocytes and HCT116 colon cancer cells\ntissue_or_cell_type: HDAC activity, protein levels and target acetylation\nexperimental_model: Matched cell-type and time-course comparison\nlimitations: Activity assays, protein abundance and substrate acetylation are distinct endpoints; mechanism of their divergence was not established. Erratum PMID 27271518 adds an omitted funding acknowledgment without revising these results.\nexposure: Sulforaphane exposure; serum and time-course comparisons\nevidence_span: {\"source_cache\": \"artifacts/sulforaphane-research/25307283.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"cc736d6c2f2dc6c4026bdad0a5835d69ed094775076a2c1606f47020e6783331\", \"start_char\": 0, \"end_char\": 1504, \"text_sha256\": \"cc736d6c2f2dc6c4026bdad0a5835d69ed094775076a2c1606f47020e6783331\"}\n[sulforaphane-p25307283] The effect of sulforaphane on histone deacetylase activity in keratinocytes: Differences between in vitro and in vivo analyses. (2015). https://pubmed.ncbi.nlm.nih.gov/25307283/ DOI: 10.1002/mc.22224","model_system":"Matched cell-type and time-course comparison","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [sulforaphane-p25307283] The effect of sulforaphane on histone deacetylase activity in keratinocytes: Differences between in vitro and in vivo analyses. (2015). https://pubmed.ncbi.nlm.nih.gov/25307283/ DOI: 10.1002/mc.22224","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"a4bafbf7-f117-53c9-a6d7-8fb25e4aca72","stable_key":"import-44eaeae5-557a-552b-8998-884f30462e2a","title":"Sulforaphane: formation, electrophile sensing and nutrient connections (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":"f355c492a6c35673d8260b1328667fe206e5315b9fcaa5aeff53d80373c7ef97","revision_id":"f2c47d71-34cd-5160-8e92-fe196b576707","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[{"id":"3aa95785-3b8a-5532-9907-39884276c1a5","title":"Histone acetylation after sulforaphane: increased in one study, decreased in another","kind":"contradiction","status":"open","why":"The 2004 study reported increased histone acetylation in HEK293 and HCT116 cells; the 2014-online/2015-print HCT116/HaCaT comparison reported decreased H3/H4 acetylation despite lower HDAC protein. HCT116 occurs in both studies. Exposure time, serum, metabolite formation, cell state and assay endpoints differ and may help explain the opposing directions, but none is established here as the resolution. The HaCaT HDAC-activity null alone is not the disagreement.","resolution":"Retain both experimental results and compare matched HCT116 exposures and direct acetylation measurements. Do not present sulforaphane as a universal histone-acetylation increaser.","created_at":"2026-09-18 00:09:22","record_type":"conflict","display_label":"Recorded conflict","record_url":"/conflicts/3aa95785-3b8a-5532-9907-39884276c1a5","sides":[{"conflict_id":"3aa95785-3b8a-5532-9907-39884276c1a5","ordinal":0,"label":"Increased acetylation, including HCT116","revision_id":"f2c47d71-34cd-5160-8e92-fe196b576707","start_line":593,"end_line":604,"quote":"### sulforaphane-histone-acetylation-up\nSulforaphane exposure increased acetylated histones in HEK293 and HCT116 experiments, including increased acetylated histones at the HCT116 P21 promoter.\nCondition category: normal\nnutrient_topic: Sulforaphane research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The study measured a change to the chemical marks on DNA-packaging proteins.\norganism: Human HEK293 and HCT116 cells\ntissue_or_cell_type: Histone deacetylase activity and histone acetylation\nexperimental_model: Cell exposure, enzyme assays, metabolites and chromatin immunoprecipitation\nlimitations: High-level HDAC activity was measured without establishing universal isoform inhibition; cell effects are not cancer-treatment outcomes.\nexposure: Parent SFN, SFN-GSH, SFN-Cys and SFN-NAC; GST inhibition\nevidence_span: {\"source_cache\": \"artifacts/sulforaphane-research/15313918.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"9478957b1513e25cb47f13d6a1aca0df542fc851d8eb4b9c6394010e90dbe83e\", \"start_char\": 0, \"end_char\": 1861, \"text_sha256\": \"9478957b1513e25cb47f13d6a1aca0df542fc851d8eb4b9c6394010e90dbe83e\"}\n[sulforaphane-p15313918] A novel mechanism of chemoprotection by sulforaphane: inhibition of histone deacetylase. (2004). https://pubmed.ncbi.nlm.nih.gov/15313918/ DOI: 10.1158/0008-5472.can-04-1326","source_key":"import-44eaeae5-557a-552b-8998-884f30462e2a","source_title":"Sulforaphane: formation, electrophile sensing and nutrient connections (2026-09-17)","claim_ids":["b309c749-2cf0-5dd5-8008-919d0965ce75"]},{"conflict_id":"3aa95785-3b8a-5532-9907-39884276c1a5","ordinal":1,"label":"Decreased acetylation markers in HCT116/HaCaT comparison","revision_id":"f2c47d71-34cd-5160-8e92-fe196b576707","start_line":606,"end_line":617,"quote":"### sulforaphane-histone-acetylation-down\nSulforaphane decreased acetylated histone H3, H4 and tubulin markers in the cell comparisons despite reduced HDAC protein levels.\nCondition category: normal\nnutrient_topic: Sulforaphane research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Less enzyme protein did not produce the expected increase in acetylation.\norganism: Human HaCaT keratinocytes and HCT116 colon cancer cells\ntissue_or_cell_type: HDAC activity, protein levels and target acetylation\nexperimental_model: Matched cell-type and time-course comparison\nlimitations: Activity assays, protein abundance and substrate acetylation are distinct endpoints; mechanism of their divergence was not established. Erratum PMID 27271518 adds an omitted funding acknowledgment without revising these results.\nexposure: Sulforaphane exposure; serum and time-course comparisons\nevidence_span: {\"source_cache\": \"artifacts/sulforaphane-research/25307283.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"cc736d6c2f2dc6c4026bdad0a5835d69ed094775076a2c1606f47020e6783331\", \"start_char\": 0, \"end_char\": 1504, \"text_sha256\": \"cc736d6c2f2dc6c4026bdad0a5835d69ed094775076a2c1606f47020e6783331\"}\n[sulforaphane-p25307283] The effect of sulforaphane on histone deacetylase activity in keratinocytes: Differences between in vitro and in vivo analyses. (2015). https://pubmed.ncbi.nlm.nih.gov/25307283/ DOI: 10.1002/mc.22224","source_key":"import-44eaeae5-557a-552b-8998-884f30462e2a","source_title":"Sulforaphane: formation, electrophile sensing and nutrient connections (2026-09-17)","claim_ids":["7abad7cb-33be-5d01-9c17-06699bb91949"]}]}],"corrections":[],"research":null}