Institute of Microbial Chemistry (BIKAKEN), Numazu Branch, Microbial Chemistry Research Foundation, Numazu, 410-0301, Japan.
Institute of Microbial Chemistry (BIKAKEN), Laboratory of Oncology, Microbial Chemistry Research Foundation, Shinagawa-ku, 141-0021, Japan.
Oncol Res. 2023 Sep 15;31(6):845-853. doi: 10.32604/or.2023.030266. eCollection 2023.
The androgen receptor (AR) is a critical target in all the clinical stages of prostate cancer. To identify a new AR inhibitor, we constructed a new screening system using the androgen-dependent growth of prostate cancer cell lines as a screening indicator. We screened 50,000 culture broths of microorganisms using this screening system and found that the fermentation broth produced by a fungus inhibited androgen-dependent growth of human prostate cancer LNCaP cells without cytotoxicity. Purification of this culture medium was performed, and this resulted in deoxynortryptoquivaline (DNT) being identified as a novel inhibitor of AR function. DNT showed potent inhibition of androgen-dependent growth of human prostate cancer LNCaP cells. The AR competitor assay was performed, and DNT did not act as an AR antagonist. However, DNT inhibited AR-dependent transcriptional activity and AR nuclear translocation, it suggested that the suppression of AR function leads to inhibition activity against androgen-dependent growth.
雄激素受体（AR）是前列腺癌所有临床阶段的关键靶点。为了鉴定新的 AR 抑制剂，我们构建了一个新的筛选系统，使用前列腺癌细胞系的雄激素依赖性生长作为筛选指标。我们使用该筛选系统筛选了 50,000 个微生物培养物的培养物，并发现一种真菌产生的发酵液抑制了人前列腺癌细胞 LNCaP 的雄激素依赖性生长，而没有细胞毒性。对该培养基进行了纯化，结果鉴定出脱氧诺托匹汀（DNT）为 AR 功能的新型抑制剂。DNT 对人前列腺癌细胞 LNCaP 的雄激素依赖性生长具有强烈的抑制作用。进行了 AR 竞争测定，结果表明 DNT 不作为 AR 拮抗剂。但是，DNT 抑制了 AR 依赖性转录活性和 AR 核易位，这表明抑制 AR 功能会导致对雄激素依赖性生长的抑制活性。
