Cellular Targets of Dietary Polyphenol Resveratrol

摘要

To test the hypothesis that resveratrol, a grape derived polyphenol, exerts its chemopreventive properties against prostate cancer by interacting with specific cellular targets, denoted resveratrol targeting proteins (RTPs). To explore the existence of RTPs in androgen-dependent LNCaP and androgen- independent (PC-3) cells, by chemically immobilizing resveratrol on epoxy- activated agarose to generate a biospecific affinity matrix for isolating and purifying RTPs from cell extracts. By combining resveratrol affinity chromatography with MALDI-TOF mass spectrometry, we have identified dihydronicotinamid eriboside:quinone reductase (NQO2) as a distinct RTP from LNCaP and PC-3 cells. As mentioned in the annual report, we are in the process of possibly identifying another RTP. This goal has been achieved in PC-3 cell extracts by combining resveratrol affinity column chromatography with mass spectrophotometry. The second RTP is glutathione sulfotransferase GST-Pi. We have identified two resveratrol RTPs, respectively, NQO2 and GST-Pi, both with function in detoxification reactions. Our findings suggest that resveratrol might function as a chemopreventive agent by interacting and modulating activity and/or stability of detoxification enzymes.