Resveratrol regulates IGF-II in MCF-7 human breast cancer cells

2874

Some dietary factors significantly influence the incidence and progression of breast cancer. One potential candidate is Resveratrol, a phytoalexin or antibiotic compound produced as part of a plant defense system against disease. IGF-II (Insulin-like Growth Factor II) plays a critical role in the growth and development of many tissues, and is thought to play a particularly prominent role in tumorigenesis. We have previously shown that Resveratrol, in a dose dependent manner, regulates IGF-II mRNA and protein level secreted into the media of treated MCF-7 breast cancer cells. Resveratrol also modulates cathepsin D (a lysosomal enzyme that also binds the IGF-II/M6P receptor), secretion into the media of the same cell line, but not its mRNA. The modulation of cathepsin D is mediated by IGF-II. These effects were not observed in MCF-10 breast epithelial cells. Our hypothesis is that Resveratrol effect on MCF-7 cell proliferation is mediated by its dose dependent regulation of IGF-II levels. Our present study shows a significant increase in cell number and BrdU incorporation in MCF-7 cells treated with Resveratrol at a concentration of 10^-6 M; while Resveratrol concentration of 10^-4 M significantly inhibited cell proliferation and BrdU incorporation in the same cell line. Interestingly, in MCF-10 cells, 10^-6 M Resveratrol did not affect IGF-II mRNA/protein levels and subsequently cell proliferation. Since Resveratrol is proposed to be a chemical with potential chemopreventive use it is significant that its effects may be mediated by IGF-II, which is a peptide that regulates cell motility, angiogenesis, inhibits apoptosis and increases cell proliferation. Our studies will have significant clinical implications at the same time that allow us to characterize the mechanism of action of Resveratrol in breast cancer.