A54

Retinoids are known for their role in regulating cell growth and proliferation and for activating tumor suppressor genes. We have previously shown that Retinoid X Receptor alpha (RXR alpha) is silenced in tumors of the colon cancer AOM-APCmin+ mouse model. Upon treatment with green tea, RXR alpha expression was restored and intestinal tumorigenesis was inhibited. We hypothesize that tea polyphenols, especially epigallocatechin gallate (EGCG), induce modification of gene expression through effects of DNA methyltransferases (DNMTs). We first determined the optimal range of EGCG concentration with which to treat the cells by performing cytotoxcity assays. We treated HT-29 and HCT116 colon cancer cells with EGCG concentrations of 0, 50, 100 or 150µM for 24 and 48 hours. The cell lines were chosen based on their methylation status. HCT116 cells are sensitive to methylation while HT-29 cells are not. Using nuclear fractions of the cell lysates, we probed for presence of the most common DNMTs using western blotting. We found that expression of DNMT1, DNMT3a and DNMT3b was inhibited in a dose dependent manner following treatment with EGCG at both 24 and 48 hour time points. We also used the DNMT inhibitor 5-aza-2dC as a positive control to recover DNMT expression in the cells treated with EGCG. We can conclude that the silencing of RXR alpha may be due in part to by repressing effects of EGCG on DNMT activity.

Citation Information: Cancer Prev Res 2008;1(7 Suppl):A54.

Seventh AACR International Conference on Frontiers in Cancer Prevention Research-- Nov 16-19, 2008; Washington, DC