A novel antiandrogen, compound 30, suppresses castration-resistant and MDV3100-resistant prostate cancer growth In Vitro and In Vivo

Hidetoshi Kuruma, Hiroaki Matsumoto, Masaki Shiota, Jennifer Bishop, Francois Lamoureux, Christian Thomas, David Briere, Gerrit Los, Martin Gleave, Andrea Fanjul, Amina Zoubeidi

研究成果: Contribution to journalArticle査読

71 被引用数 (Scopus)

抄録

Resistance to antiandrogen drugs, like MDV3100, occurs in patients with castration-resistant prostate cancer (CRPC). Thus, preventing or treating antiandrogen resistance is a major clinical challenge. We identified a novel antiandrogen, Compound 30, and compared its efficacy with MDV3100. We found that Compound 30 inhibits androgen receptor (AR) activity in LNCaP cells, C4-2 cells, as well as MDV3100-resistant cell lines. Compared with MDV3100, Compound 30 treatment induces greater reduction in AR, prostate-specific antigen (PSA), and AR transcriptional activity, and prevents AR nuclear translocation in AR-sensitive LNCaP cells. Compound 30 has antiproliferative effects in LNCaP cells, in castrate-resistant C4-2 cells, and those resistant to MDV3100. Compound 30 was equally as effective as MDV3100 in reducing tumor volume and PSA in vivo. More importantly, Compound 30 is effective at inhibiting AR activity in MDV3100-resistant cell lines and significantly prevented tumor growth and PSA increases in mice bearing MDV3100-resistant xenografts. Together, our data show that Compound 30 strongly inhibited AR activity and suppressed castration-resistant LNCaP growth as well as MDV3100-resistant cell growth in vitro and in vivo. These data provide a preclinical proof-of-principle that Compound 30 could be a promising next generation anti-AR agent, especially in the context of antiandrogen-resistant tumors.

本文言語英語
ページ(範囲)567-576
ページ数10
ジャーナルMolecular cancer therapeutics
12
5
DOI
出版ステータス出版済み - 5 2013
外部発表はい

All Science Journal Classification (ASJC) codes

  • 腫瘍学
  • 癌研究

フィンガープリント

「A novel antiandrogen, compound 30, suppresses castration-resistant and MDV3100-resistant prostate cancer growth In Vitro and In Vivo」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル