Grape Polyphenol Signaling to Regulate Breast Cancer Metastasis

The cancer preventive properties of individual grape and red wine polyphenols have been investigated. However, such studies focus mainly on individual compounds at concentrations too high to be achieved by dietary intake. In this study, we proposed to test the hypothesis that combined grape and red wine polyphenols at low concentrations can be more effective than individual compounds at inhibition of breast cancer progression. For this, we tested the effects of resveratrol, quercetin, and catechin, which constitute 70 of red wine polyphenols, on biological processes relevant to breast cancer progression using breast cancer cell lines. We found that combined grape polyphenols induce apoptosis and are more effective than individual resveratrol, quercetin, or catechin at inhibition of cell functions that promote breast cancer progression. Using estrogen receptor ERalpha-, ERbeta MDA-MB-231 and ER- MDA-MB-435 breast cancer cell lines we demonstrated that combined grape polyphenols increased apoptosis and inhibited cell proliferation, cell cycle progression, and cell migration. Work in the laboratory also showed that combined grape polyphenols reduced primary breast tumor growth and metastasis in nude mice Castillo-Pichardo, et al., 2009, Clin. Exp. Met. 26505-16. Studies are underway to identify the molecular targets of grape polyphenols in breast cancer.