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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Abietanes / chemical synthesis
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Abietanes / chemistry
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Abietanes / pharmacology*
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Androgen Antagonists / chemical synthesis
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Androgen Antagonists / chemistry
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Androgen Antagonists / pharmacology*
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Antineoplastic Agents / chemical synthesis
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology*
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Apoptosis / drug effects
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Cell Line, Tumor / drug effects
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Humans
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Male
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Mutation
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Prostate-Specific Antigen / metabolism
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Prostatic Neoplasms / pathology*
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Receptors, Androgen / genetics
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Receptors, Androgen / metabolism*
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Serpins / biosynthesis*
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Structure-Activity Relationship
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Transcriptional Activation / drug effects
Substances
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Abietanes
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Androgen Antagonists
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Antineoplastic Agents
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Receptors, Androgen
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SERPIN-B5
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Serpins
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tanshinone
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Prostate-Specific Antigen