Action mechanism elucidation of DNT, anti-prostatecancer agent from natural products

2014 Fiscal Year Final Research Report

• Project/Area Number: 24592417
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Urology
• Research Institution: Microbial Chemistry Research Foundation
• Principal Investigator: YAMAZAKI Yohko 公益財団法人微生物化学研究会, 微生物化学研究所 沼津支所, 研究員 (80342690)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 去勢抵抗性前立腺がん / アンドロゲンレセプター

Outline of Final Research Achievements

Endocrine therapy (androgen ablation) is the main treatment for advanced prostate cancer. Despite an initial efficacy of androgen deprivation therapy, prostate cancer progress within a few years from androgen-dependent to castration- resistant (CRPC) disease in most of the patients. Although AR still plays an essential role in CRPC, AR inhibitor is only an antagonist.
We hypothesized that a new type AR inhibitor could serve as a unique therapeutic agent for prostate cancer. To identify a new type AR inhibitor, we screened cultured broths of microorganisms and found that small molecule compound N-deoxynortryptoquivaline (DNT), a novel inhibitor of AR function, showed potent inhibition against androgen-dependent proliferation of LNCaP prostate cancer cells. DNT showed significant inhibition of AR nuclear translocation and against androgen-dependent proliferation of LNCaP cells.

Free Research Field

去勢抵抗性前立腺がんおけるアンドロゲンレセプター機能阻害剤の開発