Abstract
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 (RXRα) is silenced in tumors of the colon cancer AOM‐APCMin/+ mouse model. Upon treatment with green tea, RXR 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) as well as Histone Deacetylases (HDACs). We treated HT‐29 and HCT116 colon cancer cells with EGCG concentrations of 0, 50, 100 or 150µM or 5µM of the DNMT inhibitor 5‐aza‐2dC for 48, 72 and 96 hours as well as for two, three and four doubling times. The cell lines were chosen based on their methylation status. HCT116 cells are more sensitive to promoter region methylation compared to HT‐29 cells. Using nuclear fractions of the cell lysates, we probed for presence of the most common DNMTs and HDACs using western blotting. We found that expression of DNMTs as well as HDACs was inhibited in a dose dependent manner following treatment with EGCG. We also found that treatments according to doubling times showed a more profound difference in expression levels when compared to traditional time points. 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. This could be one potential mechanism of cancer chemoprevention in green tea that outlines a new epigenetic pathway.
Citation Information: Mol Cancer Ther 2009;8(12 Suppl):A95.
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