Abstract A50: Black raspberry treatment in FAP patients shows re-expression of methylation-silenced genes

Abstract

Abstract In a clinical trial, we found that freeze-dried black raspberry (BRB) powder reduced the number of rectal polyps in patients with familial adenomatous polyposis (FAP). The present study was undertaken to determine if the berries influenced the growth and apoptosis of cells in rectal polyps. In addition, because the p16 tumor suppressor gene is inactivated by methylation in greater than 60 percent of colon tumors, we examined the levels of both p16 and of DNA methyltransferase 1 (DNMT1) expression in normal and polyp specimens. DNMT1 has been shown to be overly expressed in cultured human colon cancer cell lines and this correlated with silencing of the p16 gene. Polyps and normal tissues were obtained from FAP patients before and after 36 weeks of berry treatment. Immunohistochemical staining for Ki-67 and c-MYC showed that cell proliferation was significantly reduced by berry treatment in both normal rectum and in rectal polyps. TUNEL staining for apoptosis was observed to increase significantly in both normal rectum and in rectal polyps. There was a significant decrease in DNMT1 expression and an increase in p16 expression in berry-treated normal and polyp specimens. These results suggest that nine months of black raspberry treatment resulted in reduced cell proliferation, increased apoptosis and p16 gene expression and decreased DNMT1 expression in both normal and polyp specimens taken from FAP patients. The p16/DNMT1 data suggest that black raspberries may act as a demethylating agent and should be further evaluated for their effects on the methylation status of other candidate tumor suppressor genes in colonic polyps and tumors. This research was supported by NCI grant CA103180 and USDA grant 38903-03560. Citation Information: Cancer Prev Res 2010;3(1 Suppl):A50.