Grape Powder Supplementation Attenuates Prostate Neoplasia Associated with Pten Haploinsufficiency in Mice Fed High-Fat Diet

Scope Previous studies have identified potent anticancer activities of polyphenols in preventing prostate cancer. The aim of the current study is to evaluate the chemopreventive potential of grape powder (GP) supplemented diets in genetically predisposed and obesity-provoked prostate cancer. Methods and results Prostate-specificPtenheterozygous (Pten(+/f)) transgenic mice are fed low- and high-fat diet (LFD and HFD, respectively) supplemented with 10% GP for 33 weeks, ad libitum. Prostate tissues are characterized using immunohistochemistry and western blots, and sera are analyzed by ELISA and qRT-PCR.Pten(+/f)mice fed LFD and HFD supplemented with 10% GP show favorable histopathology, significant reduction of the proliferative rate of prostate epithelial cells (Ki67), and rescue of PTEN expression. The most potent protective effect of GP supplementation is detected against HFD-induced increase in inflammation (IL-1 beta; TGF-beta 1), activation of cell survival pathways (Akt, AR), and angiogenesis (CD31) inPten(+/f)mice. Moreover, GP supplementation reduces circulating levels of oncogenic microRNAs (miR-34a; miR-22) inPten(+/f)mice. There are no significant changes in body weight and food intake in GP supplemented diet groups. Conclusions GP diet supplementation can be a beneficial chemopreventive strategy for obesity-related inflammation and prostate cancer progression. Monitoring serum miRNAs can facilitate the non-invasive evaluation of chemoprevention efficacy.