Antitumor and antimetastatic activities of grape skin polyphenols in a murine model of breast cancer

Abstract

Treatment modalities are not effective once breast cancer metastasis has occurred. Dietary botanicals may have a better protective effect. We therefore investigated the effects of grape skin polyphenols on a highly metastatic mouse mammary carcinoma cell line. In vitro treatment of 4T1 cells, with grape skin polyphenols resulted in inhibition of the migration and viability in a dose-dependent manner. The migration of 4T1 cells was significantly inhibited by grape skin polyphenols, even at a very low concentration (5μg/ml), and was totally inhibited when the concentration was 20μg/ml. However, 20μg/ml of grape skin polyphenols inhibited cell viability by only 11.4%. The inhibition of migration is independent of decreased cell viability or apoptosis induction. Further analysis indicated that the inhibition of migration by grape skin polyphenols is involved in blocking the PI3k/Akt and MAPK pathways. The effects of dietary grape skin polyphenols were then examined using an in vivo model in which 4T1 cells were implanted subcutaneously in Balb/c mice. The metastasis of tumor cells to the lungs was inhibited significantly by dietary grape skin extracts (0.5 and 1.0mg/ml in drinking water) and the survival of the mice enhanced. These data suggest that grape skin polyphenols possess chemotherapeutic efficacy against breast cancer with metastases.