Abstract 3466: Can grape powder supplemented diet prevent prostate cancer progression

Abstract

Abstract Epidemiological and experimental studies suggest a correlation between diet, particularly fat consumption and the risk of developing prostate cancer (PCa). In previous studies, we reported that stilbenes, namely resveratrol and pterostilbene, restrained prostatic intraepithelial neoplasia (PIN) formation and reduced tumor development and progression in mice models of PCa with high expression of metastasis-associated protein 1 (MTA1), an epigenetic modifier involved in the regulation of prostate cancer progression and metastasis. In this report, we evaluated three major aspects: 1) whether altering diet [low fat diet (LFD) versus high fat diet (HFD)] affects PCa progression; 2) whether grape powder (GP) supplementation to the diets protects against PCa progression, and 3) whether MTA1 targeting is the main mechanism of action. We addressed these questions by utilizing the prostate-specific (PB-Cre4) Pten heterozygous transgenic mice (Pten+/f), which mimic slow-growing PCa progression in humans. Upon accumulating 56 mice of desired genotype, we randomized mice in two major groups and fed them ad libitum with either LFD or HFD. Each of these diets contained either 0% GP or 10% GP supplementation. The same groups were assigned for control wild-type (WT) mice (Pten+/f; Cre-). After 33 weeks on corresponding diets, mice were sacrificed and urogenital system was collected for histological and immunochemical analysis. In addition, protein and RNA was isolated from the prostate tissues for molecular analysis. Blood was also collected for cytokines evaluation and pharmacokinetic analysis. The results demonstrated the following beneficial effects of GP supplementation: LFD and HFD - fed Pten+/f mice showed added favorable histopathology (H&E), intact basal layer (SMA) and luminal cells (CK-8); significant reduction of the proliferative rate of prostate epithelial cells (Ki67); non-significant trend for reducing HFD-induced MTA1 expression in Pten+/f and WT mice; protective effects against “bad” genotype and HFD-induced activation of Akt pathway; attenuation of HFD-associated increase in AR levels in both Pten+/f and WT mice; reduction of HFD-provoked increased inflammation marker IL-1β levels; non-significant trend for reducing angiogenesis (CD31; VEGF-C) in Pten+/f mice; and trend towards decreasing inflammatory TGFβ1 expression in Pten+/f mice. Curious results were obtained concerning the effect of GP on apoptosis. There were no significant changes in body weight, food intake or fat intake in GP supplemented diets groups. Citation Format: Tanvi Joshi, Ishani Patel, Avinash Kumar, Virginia Donovan, Anait S. Levenson. Can grape powder supplemented diet prevent prostate cancer progression [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3466.