{"id":"5e36076a-e768-5570-85e8-595133727306","stable_key":"c953cca8-774f-596d-b27a-f13c2c0b5fce:dhc-androgen-receptor-inhibition","predicate":"inhibits","statement":"Dihydrocapsaicin induced proliferation suppression in human prostate cancer cells by hindering the cell cycle at the G0/G1 phase, probably inhibited androgen receptor activity by blocking its movement from the cytoplasm to the nucleus through binding to the receptor ligand-binding domain, and mechanistically facilitated androgen receptor release from a stabilizing chaperone complex and enhanced its ubiquitination by E3 ligases resulting in partial degradation via the ubiquitin-proteasome pathway, while also reducing tumour growth in vivo.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"3fc88bc5-d8f0-56ab-a236-77753ef46d11","mechanism_event_label":"It stops the hormone receptor that drives prostate cancer from reaching the nucleus, and marks it for disposal.","subject":{"id":"6259a8e0-9611-5f60-9e1b-53bbd8eb1afd","slug":"dihydrocapsaicin","display_name":"Dihydrocapsaicin","entity_type_key":"small_molecule"},"object":{"id":"b56985c9-da40-503a-8563-85aaf1881e47","slug":"ar","display_name":"Human androgen receptor / AR","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"3fc88bc5-d8f0-56ab-a236-77753ef46d11","stable_key":"c953cca8-774f-596d-b27a-f13c2c0b5fce:dhc-androgen-receptor-inhibition-event","event_type":"biochemical_relationship","label":"It stops the hormone receptor that drives prostate cancer from reaching the nucleus, and marks it for disposal.","description":"Dihydrocapsaicin induced proliferation suppression in human prostate cancer cells by hindering the cell cycle at the G0/G1 phase, probably inhibited androgen receptor activity by blocking its movement from the cytoplasm to the nucleus through binding to the receptor ligand-binding domain, and mechanistically facilitated androgen receptor release from a stabilizing chaperone complex and enhanced its ubiquitination by E3 ligases resulting in partial degradation via the ubiquitin-proteasome pathway, while also reducing tumour growth in vivo.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"8ac5bf16-c076-50c1-81b7-05e1abe6a7e1","slug":"ar-nuclear-translocation","display_name":"Movement of the androgen receptor from cytoplasm to nucleus","entity_type_key":"cellular_process"},"role":"blocked_process","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"67d9c6c9-ff74-5b27-960e-3dc5104e5e16","slug":"ar-ligand-binding-domain","display_name":"The ligand-binding domain of the androgen receptor","entity_type_key":"protein_state"},"role":"proposed_site","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"cdeb28c7-1f5b-5616-83db-603d50bb866f","slug":"prostate-cancer-proliferation","display_name":"Proliferation of human prostate cancer cells","entity_type_key":"cellular_process"},"role":"suppressed_process","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"6259a8e0-9611-5f60-9e1b-53bbd8eb1afd","slug":"dihydrocapsaicin","display_name":"Dihydrocapsaicin","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"b56985c9-da40-503a-8563-85aaf1881e47","slug":"ar","display_name":"Human androgen receptor / AR","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/dihydrocapsaicin-research/41045970.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"232b30793c88e9e8fca6110ff6390d2d343ed78114d2daf849984cf2d2b80981\", \"start_char\": 0, \"end_char\": 1566, \"text_sha256\": \"232b30793c88e9e8fca6110ff6390d2d343ed78114d2daf849984cf2d2b80981\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human prostate cancer cell lines with in vivo tumour growth and in silico binding analysis","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Dihydrocapsaicin applied to human prostate cancer cells and to xenografts","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Combines cell, animal and computational arms. The binding to the ligand-binding domain is in silico and is recorded as such.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin.","comparator":null,"unit":null,"notes":"","entity":{"slug":"dihydrocapsaicin","display_name":"Dihydrocapsaicin","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Human cells and mouse","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"It stops the hormone receptor that drives prostate cancer from reaching the nucleus, and marks it for disposal.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[dhc-p41045970] Androgen receptor inhibitory activity of dihydrocapsaicin: Insights from in vitro, in vivo and in silico studies. (2026). https://pubmed.ncbi.nlm.nih.gov/41045970/ DOI: 10.1016/j.jsbmb.2025.106872","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Prostate cancer","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"524732ed-19cc-56e9-90f4-a3e572b3888f","evidence_kind":"source_excerpt","locator":"Lines 751-762","start_line":751,"end_line":762,"excerpt":"### dhc-androgen-receptor-inhibition\nDihydrocapsaicin induced proliferation suppression in human prostate cancer cells by hindering the cell cycle at the G0/G1 phase, probably inhibited androgen receptor activity by blocking its movement from the cytoplasm to the nucleus through binding to the receptor ligand-binding domain, and mechanistically facilitated androgen receptor release from a stabilizing chaperone complex and enhanced its ubiquitination by E3 ligases resulting in partial degradation via the ubiquitin-proteasome pathway, while also reducing tumour growth in vivo.\nCondition category: normal\nnutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin.\nplain_language: It stops the hormone receptor that drives prostate cancer from reaching the nucleus, and marks it for disposal.\norganism: Human cells and mouse\ntissue_or_cell_type: Prostate cancer\nexperimental_model: Human prostate cancer cell lines with in vivo tumour growth and in silico binding analysis\nlimitations: Combines cell, animal and computational arms. The binding to the ligand-binding domain is in silico and is recorded as such.\nexposure: Dihydrocapsaicin applied to human prostate cancer cells and to xenografts\nevidence_span: {\"source_cache\": \"artifacts/dihydrocapsaicin-research/41045970.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"232b30793c88e9e8fca6110ff6390d2d343ed78114d2daf849984cf2d2b80981\", \"start_char\": 0, \"end_char\": 1566, \"text_sha256\": \"232b30793c88e9e8fca6110ff6390d2d343ed78114d2daf849984cf2d2b80981\"}\n[dhc-p41045970] Androgen receptor inhibitory activity of dihydrocapsaicin: Insights from in vitro, in vivo and in silico studies. 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