title: Antiandrogenic, maspin induction, and antiprostate cancer activities of tanshinone IIA and its novel derivatives with modification in ring A.
abstract: Expression of metastatic suppressor maspin is lost in advanced prostate cancer. Clinically relevant mutations in androgen receptor (AR) convert antiandrogens into AR agonists, promoting prostate tumor growth. We discovered tanshinone IIA (TS-IIA) is a potent antagonist of mutated ARs and induces maspin expression through AR. TS-IIA suppressed AR expression and induced apoptosis in LNCaP cells. Syntheses of TS-IIA derivatives (1-9) revealed that the 4,4-dimethyl group at ring A is important for TS-IIA's antiandrogenic and maspin induction activities.
authors.affiliation: Segal Cancer Center and Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital, McGill University, 3755 Cote-Ste-Catherine, Road, Montreal, Quebec H3T 1E2, Canada.
authors.forename: Weiguo
authors.initials: W
authors.lastname: Liu
authors.forename: Jinming
authors.initials: J
authors.lastname: Zhou
authors.forename: Guoyan
authors.initials: G
authors.lastname: Geng
authors.forename: Qingwen
authors.initials: Q
authors.lastname: Shi
authors.forename: Francoise
authors.initials: F
authors.lastname: Sauriol
authors.forename: Jian Hui
authors.initials: JH
authors.lastname: Wu
mesh_terms: D045784:Abietanes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000726:Androgen Antagonists / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D006801:Humans; D008297:Male; D009154:Mutation; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000473:pathology*; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D015843:Serpins / Q000096:biosynthesis*; D013329:Structure-Activity Relationship; D015533:Transcriptional Activation / Q000187:drug effects
chemical_list: D045784:Abietanes; D000726:Androgen Antagonists; D000970:Antineoplastic Agents; D011944:Receptors, Androgen; C085344:SERPIN-B5; D015843:Serpins; C021751:tanshinone; D017430:Prostate-Specific Antigen