TY - JOUR
T1 - 27-Hydroxycholesterol stimulates cell proliferation and resistance to docetaxel-induced apoptosis in prostate epithelial cells
AU - Raza, Shaneabbas
AU - Meyer, Megan
AU - Schommer, Jared
AU - Hammer, Kimberly D.P.
AU - Guo, Bin
AU - Ghribi, Othman
N1 - Funding Information:
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.
Publisher Copyright:
© 2016, Springer Science+Business Media New York.
PY - 2016/2/1
Y1 - 2016/2/1
N2 - 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.
AB - 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.
KW - 27-Hydroxycholesterol
KW - Androgen receptor
KW - Benign prostatic hyperplasia
KW - Proliferation
KW - Prostate cancer
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U2 - 10.1007/s12032-015-0725-5
DO - 10.1007/s12032-015-0725-5
M3 - Article
C2 - 26732475
AN - SCOPUS:84953329733
SN - 1357-0560
VL - 33
SP - 1
EP - 9
JO - Medical Oncology
JF - Medical Oncology
IS - 2
M1 - 12
ER -