Abstract 2801: Resveratrol-Quercetin combination significantly inhibits prostate cancer in TRAMP mice

Worldwide, prostate cancer (PCa) is the second most frequently diagnosed cancer and the sixth leading cause of cancer death in males. The existing treatments as well as surgical approaches have not been fully effective in PCa management. Therefore, new mechanism-based approaches are needed for the prevention as well as therapy of PCa. Resveratrol (trans-3,5,4′-trihydroxystilbene), an antioxidant found in red grapes, has been shown to afford chemopreventive as well as therapeutic effects against several cancers. We have advocated the idea that resveratrol may be better utilized for cancer management, when given in combination with other agents. A number of in vitro and in vivo studies have suggested potential usefulness of resveratrol in PCa management. However, an important issue associated with the potential clinical/human use of resveratrol is its low in vivo bioavailability, due to its rapid metabolism (via glucuronidation, sulfation and hydroxylation). Quercetin, also a flavonoid, has been shown to inhibit in vivo sulfation of resveratrol. Interestingly, resveratrol and quercetin, both are found in red grapes and several other plants, indicating their natural association. Like resveratrol, quercetin has also been shown to inhibit PCa in animal models. In this study, we tested the hypothesis that resveratrol-quercetin combination may have better efficacy against PCa as quercetin, in addition to its own effect, can enhance the bioavailability of resveratrol via inhibiting its sulfation, thereby imparting superior anti-proliferative efficacy. We found that resveratrol-quercetin combination resulted in a superior anti-proliferative response in multiple human PCa cell lines (22Rν1, DU145 and PC3), as assessed by MTT (3-(4, 5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide) assay for cellular metabolic activity, and trypan blue exclusion analysis for cell growth and viability. Further, clonogenic survival assay, where equal number of treated cells were allowed to grow for two weeks, showed that the combination was superior to resveratrol or quercetin alone. To ascertain the in vivo relevance of in vitro data, we determined the effects of resveratrol-quercetin combination on PCa development and progression in TRAMP model, which closely mimics hallmark features of human PCa. We conducted prevention and intervention trials employing four experimental groups, 1) control (AIN76A diet), 2) resveratrol (600 mg/kg in diet), 3) quercetin (60 mg/kg in diet), and 4) resveratrol (600 mg/kg in diet) + quercetin (60 mg/kg in diet). Our data demonstrated that resveratrol-quercetin combination was markedly superior to either of the individual agents, in intervention setting when treatment was started after the onset of PCa in TRAMP mice. Further studies are ongoing in our laboratory to determine the mechanism(s) associated with the observed effect of resveratrol-quercetin combination. Citation Format: Chandra K. Singh, Nihal Ahmad. Resveratrol-Quercetin combination significantly inhibits prostate cancer in TRAMP mice. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2801. doi:10.1158/1538-7445.AM2015-2801