27-Hydroxycholesterol stimulates cell proliferation and resistance to docetaxel-induced apoptosis in prostate epithelial cells

Although the causes of prostate cancer (PCa) and benign prostatic hyperplasia (BPH) are not known, the role of oxidative stress, aging, and diet are suspected to increase the incidence of prostate complications.

The cholesterol oxidation derivative (oxysterol) 27-hydroxycholesterol (27-OHC) is the most prevalent cholesterol metabolite in the blood. As aging, oxidative stress, and hypercholesterolemia are associated with increased risk of PCa and BPH, and because 27-OHC levels are also increased with aging, hypercholesterolemia, and oxidative stress, determining the role of 27-OHC in the progression of PCas and BPH is warranted. In this study, we determined the effect of 27-OHC in human prostate epithelial cells RWPE-1. We found that 27-OHC stimulates proliferation and increases androgen receptor (AR) transcriptional activity. 27-OHC also increased prostate-specific antigen expression and enhanced AR binding to the androgen response element compared to controls. Silencing AR expression with siRNA markedly reduced the 27-OHC-induced proliferation. Furthermore, 27-OHC blocked docetaxel-induced apoptosis. Altogether, our results suggest that 27-OHC may play an important role in PCa and BPH progression by promoting proliferation and suppressing apoptosis.

Medical oncology (Northwood, London, England). 2016 Jan 05 [Epub]

Shaneabbas Raza, Megan Meyer, Jared Schommer, Kimberly D P Hammer, Bin Guo, Othman Ghribi

Department of Basic Sciences, University of North Dakota School of Medicine and Health Sciences, 501 North Columbia Road, Grand Forks, ND, 58202, USA., Department of Basic Sciences, University of North Dakota School of Medicine and Health Sciences, 501 North Columbia Road, Grand Forks, ND, 58202, USA., Department of Basic Sciences, University of North Dakota School of Medicine and Health Sciences, 501 North Columbia Road, Grand Forks, ND, 58202, USA., Department of Veteran Affairs, Fargo VA Health Care System, Fargo, ND, 58102, USA., Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND, 58108, USA., Department of Basic Sciences, University of North Dakota School of Medicine and Health Sciences, 501 North Columbia Road, Grand Forks, ND, 58202, USA. 

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