The androgen receptor (AR) is an important therapeutic target for all clinical states of prostate cancer. We screened cultured broths of microorganisms for their ability to suppress androgen-dependent growth of human prostate cancer LNCaP and VCaP cells without cytotoxicity. We have already identified androprostamine A (APA) from a Streptomyces culture broth as a functional inhibitor of AR. APA repressed R1881 (the synthetic androgen methyltrienolone)-induced androgen-regulated gene expression and dramatically inhibited R1881-induced prostate-specific antigen levels. However, APA did not act as an AR antagonist and did not inhibit AR transcriptional activity. Moreover, AS2405, an APA derivative, significantly inhibited the growth of VCaP cells in SCID mice upon oral administration.

雄激素受体 (AR) 是前列腺癌所有临床状态的重要治疗靶点。我们筛选了培养的微生物肉汤，因为它们能够抑制人前列腺癌 LNCaP 和 VCaP 细胞的雄激素依赖性生长而没有细胞毒性。我们已经从链霉菌培养液中鉴定出雄前列胺 A (APA) 作为 AR 的功能性抑制剂。APA 抑制 R1881（合成雄激素甲基三烯酚酮）诱导的雄激素调节基因表达，并显着抑制 R1881 诱导的前列腺特异性抗原水平。然而，APA 不充当 AR 拮抗剂，也不抑制 AR 转录活性。此外，APA 衍生物 AS2405 在口服给药后显着抑制 SCID 小鼠 VCaP 细胞的生长。