Abstract A40: Epigenetic modification of human colon cancer by the green tea polyphenol EGCG

Abstract

Silencing of regulatory genes through hypermethylation of CpG islands is an important mechanism in tumorigenesis of numerous cancers. We have previously shown that Retinoid X Receptor alpha (RXRα) is silenced in tumors of the colon cancer AOM-APC/min+ mouse model. Upon treatment with green tea, RXRα expression was restored and intestinal tumorigenesis was inhibited. We examined human colonic tumor microarrays by immunohistochemcial staining and found a marked decrease in RXR expression in tumor tissue compared to normal matched tissues, inversely β-Catenin levels increased. To determine how RXRα loss is reversed in human cancers by green tea, we treated HT-29 (methylation insensitive) and HCT116 (methylation sensitive) human colon cancer cell lines with different concentrations of Epigallocatechin gallate (EGCG - major polyphenolic compound in green tea). We found by western blotting nuclear protein fractions that EGCG can restore RXRα levels in HCT116 cells in a dose dependant manner. Using these same lysates, we probed for presence of the most common DNA Methyltransferases (DNMTs) and Histone Deacetylases (HDACs). We found that expression of DNMTs as well as HDACs was inhibited in a dose dependent manner following treatment with EGCG. Additionally we examined by real time PCR, the message levels of DNMTs in cells treated with EGCG to determine if they correlate with the observed downregulation in protein expression. We can conclude that the silencing of RXRα may be due in part to by repressing effects of EGCG on DNMT as well as HDAC activity. Our results here show that EGCG, a common dietary compound, can modulate the reversal of gene-silencing involved colon carcinogenesis and maybe a possible avenue for colon cancer therapy and demonstrates be one potential mechanism of cancer chemoprevention in green tea that outlines a new epigenetic pathway. Citation Information: Cancer Prev Res 2011;4(10 Suppl):A40.

The Power of Antioxidant: TEA CATECHIN AND BODY OXIDATIVE STRESS

“…Findings on tea consumption's impact present contradictions, with some studies indicating no association between green tea and colorectal cancer risk and others reporting a reduced risk with regular tea consumption. EGCG, a green tea polyphenol, plays a role in inhibiting key factors integral to colon cancer development [85].…”

“…It's essential to note that research in this area is ongoing, and factors like individual variations, study designs, and lifestyle differences can contribute to the complexity of the findings [85,86].…”