Abstract

Abstract The muscadine grape (Vitis rotundifolia) is native to the Southeastern United States and muscadine grape seed products are marketed as dietary supplements, based upon their antioxidant properties. Extracts from muscadine grapes contain a number of antioxidants, including resveratrol and ellagic acid; however, the natural antioxidants found in grape seed extracts are predominantly procyanidins, while the grape skin extracts contain more anthocyanins. We investigated the effect of muscadine grape seed extracts (MSE) and muscadine grape skin extracts (MSKE) on the growth of human lung, colon, prostrate, skin, brain and breast cancers as well as human leukemias. Cells were incubated with increasing concentrations (from 0.5 to 50 μg/mL) of aqueous extracts of either MSE or MSKE and the total number of cells was quantified after 7 days. Both the MSE and MSKE inhibited the growth of A549 and SK-LU-1 human lung adenocarcinoma cancer cells (81.8% inhibition at the highest concentration) and HT29 and HCT116 human colon cancer cells (80.5% inhibition at the highest dose). Similarly, extracts from both muscadine grape seeds and skins inhibited the growth of LNCaP and PC3 human prostate cancer cells. The growth of U87 and U373 human glioblastoma cells and RPMI 7951 and SKMEL28 human skin cancer cells was dose-dependently reduced by treatment with the MSE or MSKE. Human leukemia cells were also incubated with increasing concentrations of the extracts; the growth of THP-1 human acute monocytic leukemia cells, HL-60 human acute promyelocytic cells, and K562 human chronic myelogenous leukemia cells was reduced by both muscadine grape extracts (average of 74.2% inhibition at the highest dose). Both the MSE and MSKE inhibited the growth of estrogen receptor-dependent ZR-75-1, HER2 over-expressing SKBR3, and triple negative MDA-MB-231 human breast cancer cells. The inhibition of growth by either extract was highest in the triple negative breast cancer cells (92.6% inhibition at the highest concentration). The reduction in human breast cancer cell growth was accompanied by a significant decrease in the phosphorylation and activation of the mitogen-activated protein kinases ERK1 and ERK2; MAP kinase activities were reduced 91% by MSE and 80% by MSKE in ZR-75-1 estrogen receptor-dependent breast cancer cells and 73% by MSE and 66% by MSKE in MDA-MB-231 triple negative breast cancer cells. There were no significant differences between the effects of the grape seed extract compared to the grape skin extract with any of the cell lines. These results demonstrate that extracts from muscadine grape seeds and muscadine grape skins inhibit the growth of human lung, colon, prostate, breast, skin, brain and leukemia cells in vitro, suggesting that further studies are warranted to investigate their potential use in the prevention or treatment of cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4220. doi:10.1158/1538-7445.AM2011-4220

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