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Abstract

Asian Journal of Andrology (2009) 11: 653-661. doi: 10.1038/aja.2009.56; published online 21 September 2009.

Uptake of resveratrol and role of resveratrol-targeting protein, quinone reductase 2, in normally cultured human prostate cells

Tze-Chen Hsieh1

1 Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY 10595, USA

Correspondence: Dr Tze-Chen Hsieh, Department of Biochemistry & Molecular Biology, New York Medical College, Valhalla, NY 10595, USA Fax: +1-914-594-4058 E-mail: Tze-chen_hsieh@nymc.edu

Received 4 May 2009; Revised 27 May 2009; Accepted 12 August 2009; Published online 21 September 2009.

Abstract
Resveratrol is a dietary polyphenol espoused to have chemopreventive activity against a variety of human cancer types. We first reported that resveratrol significantly decreases the proliferation of both androgen-dependent and hormone-refractory prostate cancer cells. However, the effects of resveratrol in normal prostate epithelial and stromal cells, particularly with regard to its uptake, subcellular distribution and intracellular targets, have not been investigated. To advance the knowledge on accessibility and cellular disposition of resveratrol in prostate cells, [3H] resveratrol, fractionation of cell extracts into subcellular compartments, Western blot analysis, resveratrol affinity column chromatography and flow cytometry were used to study the uptake and intracellular distribution of resveratrol in normally cultured prostate stromal (PrSCs) and epithelial cells (PrECs). Pretreatment of both PrSCs and PrECs for 2 days with resveratrol modulated its uptake and selectively increased its distribution to the membrane and organelle compartments. Resveratrol affinity column chromatography studies showed differential expression of a previously identified resveratrol-targeting protein, quinone reductase 2 (QR2), in PrSCs and PrECs. Flow cytometric analysis comparing resveratrol-treated and untreated PrSCs showed a large decrease in G1-phase and a concomitant increase in S and G2/M-phases of the cell cycle. These results suggest that resveratrol suppresses PrSC proliferation by affecting cell cycle phase distribution, which may involve the participation by QR2.

Keywords: affinity column chromatography, prostate epithelial cells, prostate stromal cells, quinone reductase 2, resveratrol

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