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

Grossebrummel,Hannah; Peter,Tilmann; Mandelkow,Robert; Weiss,Martin; Muzzio,Damian; Zimmermann,Uwe; Walther,Reinhard; Jensen,Federico; Knabbe,Cornelius; Zygmunt,Marek; Burchardt,Martin; Stope,Matthias B.

doi:10.3892/ijo.2015.3274

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

Authors:
- Hannah Grossebrummel
- Tilmann Peter
- Robert Mandelkow
- Martin Weiss
- Damian Muzzio
- Uwe Zimmermann
- Reinhard Walther
- Federico Jensen
- Cornelius Knabbe
- Marek Zygmunt
- Martin Burchardt
- Matthias B. Stope
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Affiliations: Department of Urology, University Medicine Greifswald, D-17475 Greifswald, Germany, Department of Obstetrics and Gynaecology, University Medicine Greifswald, D-17475 Greifswald, Germany, Department of Medical Biochemistry and Molecular Biology, University Medicine Greifswald, D-17475 Greifswald, Germany, Institute for Laboratory and Transfusion Medicine, Heart and Diabetes Center North Rhine-Westphalia, Ruhr University Bochum, D-32545 Bad Oeynhausen, Germany
Published online on: November 27, 2015 https://doi.org/10.3892/ijo.2015.3274
Pages: 793-800

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Abstract

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 β (TGFβ). 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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