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Grape Powder Supplementation Attenuates Prostate Neoplasia Associated with Pten Haploinsufficiency in Mice Fed High‐Fat Diet
Author(s) -
Joshi Tanvi,
Patel Ishani,
Kumar Avinash,
Donovan Virginia,
Levenson Anait S.
Publication year - 2020
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.202000326
Subject(s) - pten , prostate cancer , prostate , angiogenesis , medicine , cancer research , inflammation , protein kinase b , endocrinology , cancer , biology , apoptosis , pi3k/akt/mtor pathway , biochemistry
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‐specific Pten heterozygous ( 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‐1β; TGF‐β1), activation of cell survival pathways (Akt, AR), and angiogenesis (CD31) in Pten +/f mice. Moreover, GP supplementation reduces circulating levels of oncogenic microRNAs (miR‐34a; miR‐22) in Pten +/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.