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

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Abstract

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.

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Acknowledgments

This work was supported by University of North Dakota School of Medicine seed grant to Othman Ghribi. The funding source had no involvement in the study design, collection, analysis or interpretation of data.

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Authors and Affiliations

  1. Department of Basic Sciences, University of North Dakota School of Medicine and Health Sciences, 501 North Columbia Road, Grand Forks, ND, 58202, USA

    Shaneabbas Raza, Megan Meyer, Jared Schommer & Othman Ghribi

  2. Department of Veteran Affairs, Fargo VA Health Care System, Fargo, ND, 58102, USA

    Kimberly D. P. Hammer

  3. Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND, 58108, USA

    Bin Guo

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  1. Shaneabbas Raza
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Correspondence to Othman Ghribi.

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Disclaimer: This material is the result of work supported with resources and the use of facilities at the Fargo VA Medical Center. The contents do not represent the views of the Department of Veterans Affairs or the United States Government.

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Raza, S., Meyer, M., Schommer, J. et al. 27-Hydroxycholesterol stimulates cell proliferation and resistance to docetaxel-induced apoptosis in prostate epithelial cells. Med Oncol 33, 12 (2016). https://doi.org/10.1007/s12032-015-0725-5

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