4.6 Article

Cytochrome P450 17A1 inhibitor abiraterone attenuates cellular growth of prostate cancer cells independently from androgen receptor signaling by modulation of oncogenic and apoptotic pathways

期刊

INTERNATIONAL JOURNAL OF ONCOLOGY
卷 48, 期 2, 页码 793-800

出版社

SPANDIDOS PUBL LTD
DOI: 10.3892/ijo.2015.3274

关键词

prostate cancer; abiraterone; cytochrome P450 17A1; apoptosis; cell cycle; transforming growth factor beta

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资金

  1. Gerhard Domagk grant of the University Medicine Greifswald, Greifswald, Germany

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Abiraterone provides significant survival advantages in prostate cancer (PC), however, the current understanding of the molecular mechanisms of abiraterone is still limited. Therefore, the abiraterone impact on androgen receptor (AR)-positive LNCaP and AR-negative PC-3 cells was assessed by cellular and molecular analyses. The present study demonstrated, that abiraterone treatment significantly decreased cell growth, AR expression, and AR activity of AR-positive LNCaP cells. Notably, AR-negative PC-3 cells exhibited comparable reductions in cellular proliferation, associated with DNA fragmentation and pro-apoptotic modulation of p21, caspase-3, survivin, and transforming growth factor beta (TGF beta). Our observations suggest that the attenuation of AR signaling is not the only rationale to explain the abiraterone anticancer activity. Abiraterone efficacy may play a more global role in PC progression control than originally hypothesized. In this regard, abiraterone is not only a promising drug for treatment of AR-negative PC stages, even more, abiraterone may represent an alternative for treatment of other malignancies besides prostate cancer.

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