The phytochemical resveratrol contained in red grapes has been shown to inhibit prostate cancer cell growth, in part, through its antioxidant activity. Muscadine grapes contain unique phytochemical constituents compared with other grapes and are potentially a source for novel compounds with antitumor activities. We compared the antitumor activities of muscadine grape skin extract (MSKE), which we show contains no resveratrol, with that of resveratrol using primary cultures of normal prostate epithelial cells (PrEC) and the prostate cancer cell lines RWPE-1, WPE1-NA22, WPE1-NB14, and WPE1-NB26, representing different stages of prostate cancer progression. MSKE significantly inhibited tumor cell growth in all transformed prostate cancer cell lines but not PrEC cells. Prostate tumor cell lines, but not PrEC cells, exhibited high rates of apoptosis in response to MSKE through targeting of the phosphatidylinositol 3-kinase–Akt and mitogen-activated protein kinase survival pathways. The reduction in Akt activity by MSKE is mediated through a reduction in Akt transcription, enhanced proteosome degradation of Akt, and altered levels of DJ-1, a known regulator of PTEN. In contrast to MSKE, resveratrol did not induce apoptosis in this model but arrested cells at the G1-S phase transition of the cell cycle associated with increased expression of p21 and decreased expression of cyclin D1 and cyclin-dependent kinase 4 proteins. These results show that MSKE and resveratrol target distinct pathways to inhibit prostate cancer cell growth in this system and that the unique properties of MSKE suggest that it may be an important source for further development of chemopreventive or therapeutic agents against prostate cancer. [Cancer Res 2007;67(17):8396–405]

Where did they get it?

Chemicals and preparation of MSKE. Resveratrol, DMSO, propidium iodide, and Z-leu-leu-leu-al (MG132 proteosome degradation inhibitor) were purchased from the Sigma Chemical. Dried and pulverized muscadine grape skin was obtained from Muscadine Products Corporation. The muscadine skin powder was prepared from the Ison cultivar, a purple-skinned variety. Similarly, dried and ground muscadine ground seeds from the Ison variety were used for the muscadine seed extract. A single, large preparation of MSKE was used for all experiments in this study. Polyphenolic compounds from the dried and pulverized muscadine grape skin were extracted with 50% ethanol/water at a nominal ratio of 9:1 (v/w) by stirring with a magnetic stir bar for 1 h at room temperature. The slurry was allowed to settle for 24 h, and the supernatant was passed through a 0.2 μmol/L membrane filter funnel (Nalgene) and collected under a vacuum.

More info below: