title: 27-Hydroxycholesterol stimulates cell proliferation and resistance to docetaxel-induced apoptosis in prostate epithelial cells.
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.
authors.affiliation: Department of Basic Sciences, University of North Dakota School of Medicine and Health Sciences, 501 North Columbia Road, Grand Forks, ND, 58202, USA.
authors.forename: Shaneabbas
authors.initials: S
authors.lastname: Raza
authors.affiliation: Department of Basic Sciences, University of North Dakota School of Medicine and Health Sciences, 501 North Columbia Road, Grand Forks, ND, 58202, USA.
authors.forename: Megan
authors.initials: M
authors.lastname: Meyer
authors.affiliation: Department of Basic Sciences, University of North Dakota School of Medicine and Health Sciences, 501 North Columbia Road, Grand Forks, ND, 58202, USA.
authors.forename: Jared
authors.initials: J
authors.lastname: Schommer
authors.affiliation: Department of Veteran Affairs, Fargo VA Health Care System, Fargo, ND, 58102, USA.
authors.forename: Kimberly D P
authors.initials: KD
authors.lastname: Hammer
authors.affiliation: Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND, 58108, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Guo
authors.affiliation: Department of Basic Sciences, University of North Dakota School of Medicine and Health Sciences, 501 North Columbia Road, Grand Forks, ND, 58202, USA. othman.ghribi@med.und.edu.
authors.forename: Othman
authors.initials: O
authors.lastname: Ghribi
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects; D006801:Humans; D006888:Hydroxycholesterols / Q000494:pharmacology*; D007610:Kallikreins / Q000235:genetics / Q000378:metabolism; D008297:Male; D011401:Promoter Regions, Genetic; D011467:Prostate / Q000166:cytology* / Q000187:drug effects; D017430:Prostate-Specific Antigen / Q000235:genetics / Q000378:metabolism; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D043823:Taxoids / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D006888:Hydroxycholesterols; D011944:Receptors, Androgen; D043823:Taxoids; D000077143:Docetaxel; C076996:27-hydroxycholesterol; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen
keywords: 27-Hydroxycholesterol; Androgen receptor; Benign prostatic hyperplasia; Proliferation; Prostate cancer