Dietary Polyphenols May Affect DNA Methylation

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Abstract
Certain dietary polyphenols, such as (−)-epigallocatechin 3-gallate (EGCG) from green tea and genistein from soybean, have been demonstrated to inhibit DNA methyltransferases (DNMT) in vitro. This inhibitory activity is associated with the demethylation of the CpG islands in the promoters and the reactivation of methylation-silenced genes such as p16INK4a, retinoic acid receptor β, O6-methylguanine methyltransferase, human mutL homolog 1, and glutathione S-transferase-π. These activities have been observed in human esophageal, colon, prostate, and mammary cancer cell lines, and the activity can be enhanced by the presence of histone deacetylase inhibitors or by a longer-term treatment. Many other polyphenolic compounds have lower activities in inhibiting DNMT. Catechol polyphenols may indirectly inhibit DNMT by generating S-adenosyl-L-homocysteine on their methylation by S-adenosyl-L-methionine. In theory, prevention or reversal of hypermethylation-induced inactivation of key tumor suppression genes or receptor genes by DNMT inhibitors could be an effective approach for cancer prevention. Because of the rather low bioavailability of most polyphenolic compounds, how much of an effect dietary polyphenols would have on DNA methylation in humans is not clear. The effect of normal dietary consumption of a single polyphenolic compound is probably insignificant. However, the combination of polyphenols with dietary histone deacetylase inhibitors and the additive effect of different dietary chemicals may produce some effects. On the other hand, the consumption of excessive amounts of polyphenols in dietary supplements may affect DNA methylation status. All these possibilities remain to be examined.