Nutrition plays a significant role on the incidence and mortality of most human cancers. In recent years, health effects of dietary polyphenols, particularly ones derived from soy, tea, and grapes, have received considerable attention. To fully realize the translational benefits of a specific polyphenols, it is imperative to have information on its mechanism(s) and identity of its cellular targets. Resveratrol is a grape derived polyphenol that has been considered a chemopreventive agent for prostate cancer (CaP). The mechanism of resveratrol is relatively unexplored. We hypothesize that resveratrol interacts with and modulates target proteins involved in chemoprevention of the neoplastic phenotype. Methodologies have limited the ability to detect proteins capable of interacting with resveratrol. To circumvent this limitation and as test of proof of the above hypothesis, resveratrol immobilized on epoxy-activated agarose beads has been explored as an innovative approach to identify cellular proteins that interact directly or indirectly with reseratrol. A 22-kDa polypeptide (tentatively named resveratrol binding protein, RBP-22) from androgen-independent PC-3 CaP cell extract has been purified to near homeogeneity, based on elution with resveratrol from this affinity matrix. These preliminary results suggest that binding to resveratrol affinity column offers a novel and target specific innovative approach to identify and purify proteins that may distinguish responsiveness of cancer from normal cells to resveratrol. To more precisely assess the role of RBP-22 in prostate carcinogenesis, our first aim will be to determine the identity of RBP-22 by mass spectrometric analysis and cloning. Polyclonal and monoclonal antibodies to the RBP-22 will be generated, with the goal of and ELISA assay. To explore the translation application of resveratrol affinity chromatography, our second aim is to analyze RBP-22 and other RBPs in CaP cells (spanning the early, androgen-sensitive (using LNCaP cells) and late, hormone-refractory (using PC-3 cells) stages of prostate cancer), with RBPs from normal prostate cells. These studies will reveal mechanism of chemoprevention of resveratrol and provide insights that accompanying the transgression of CaP from an androgen ablation treatable form to an androgen-independent state, currently without curative therapies.
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| Hsieh, Tze-Chen; Wang, Zhirong; Deng, Haiteng et al. (2008) Identification of glutathione sulfotransferase-pi (GSTP1) as a new resveratrol targeting protein (RTP) and studies of resveratrol-responsive protein changes by resveratrol affinity chromatography. Anticancer Res 28:29-36 |
