Abstract

Although the link between diet and cancer is complex, epidemiological data confirm that diet is a risk factor for prostate cancer and indicate a reduced prostate cancer incidence associated with a diet rich in vegetables and fruits. Because of the known protective effect of grape seed extract (GSE) against prostate cancer, we evaluated the effects of grape powder extract (GPE) on cell viability, proliferation, and metastatic capability. Importantly, we explored the possible novel mechanism of GPE through metastasis-associated protein 1 (MTA1) downregulation in prostate cancer, since our previous studies indicated resveratrol (Res)- and pterostilbene (Pter)-induced MTA1-mediated anticancer activities in prostate cancer. We found that GPE inhibited the cell viability and growth of prostate cancer cells only at high 100 μg/mL concentrations. However, at low 1.5–15 μg/mL concentrations, GPE significantly reduced the colony formation and wound healing capabilities of both DU145 and PC3M cells. Moreover, we found that GPE inhibited MTA1 in a dose-dependent manner in these cells, albeit with considerably less potency than Res and Pter. These results indicate that stilbenes such as Res and Pter specifically and potently inhibit MTA1 and MTA1-associated proteins compared to GPE, which contains low concentrations of Res and mainly consists of other flavonoids and anthocyanidins. Our findings support continued interest in GPE as a chemopreventive and anti-cancer agent against prostate cancer but also emphasize the unique and specific properties of stilbenes on MTA1-mediated anticancer effects on prostate cancer.

Highlights

  • Despite progresses in understanding the molecular mechanisms of prostate cancer (PCa), it is still the most frequently diagnosed cancer in men in the United States, in recent years, in which life expectancy has increased

  • Discussion studies have demonstrated thatDietary diet is aphytochemicals risk factor for PCa and of plant foodsNumerous may reduce the incidence of PCa [38,39,40]

  • Such asconsumption quercetin, curcumin, Numerous studies have demonstrated that diet is a risk factor for PCa andasconsumption of plant foods may reduce the incidence of Dietary phytochemicals such quercetin, curcumin, genistein, selenium, resveratrol, and pterostilbene have been shown to possess anti-inflammatory, foods may reduce the resveratrol, incidence ofand

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Summary

Introduction

Despite progresses in understanding the molecular mechanisms of prostate cancer (PCa), it is still the most frequently diagnosed cancer in men in the United States, in recent years, in which life expectancy has increased. Dietary bioactive polyphenols with anti-inflammatory, antioxidant, and anticancer properties have been of intense interest for use as chemopreventive agents against PCa. Dietary bioactive polyphenols with anti-inflammatory, antioxidant, and anticancer properties have been of intense interest for use as chemopreventive agents against PCa Stilbenes such as resveratrol (trans-3,5,4’-trihydroxystilbene, Res) and its natural analogs including pterostilbene (trans-3,5-dimethoxystilbene, Pter), found in grapes and berries [1,2], have attracted attention as potential pharmacological approaches for primary and clinical chemoprevention of PCa [3,4,5,6,7,8,9,10,11,12,13,14,15,16]. Grape extract, which contains a mix of various polyphenols including stilbenes, might present improved pharmacokinetics and superior pharmacological potency to stilbenes alone and may hold greater potential as a natural

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