Differential Methylation and Acetylation as the Epigenetic Basis of Resveratrol’s Anticancer Activity

Numerous studies support the potent anticancer activity of resveratrol and its regulation of key oncogenic signaling pathways. Additionally, the activation of sirtuin 1, a deacetylase, by resveratrol has been known for many years, making resveratrol perhaps one of the earliest nutraceuticals with associated epigenetic activity. Such epigenetic regulation by resveratrol, and the mechanism thereof, has attracted much attention in the past decade. Focusing on methylation and acetylation, the two classical epigenetic regulations, we showcase the potential of resveratrol as an effective anticancer agent by virtue of its ability to induce differential epigenetic changes. We discuss the de-repression of tumor suppressors such as BRCA-1, nuclear factor erythroid 2-related factor 2 (NRF2) and Ras Associated Domain family-1α (RASSF-1α) by methylation, PAX1 by acetylation and the phosphatase and tensin homologue (PTEN) by both methylation and acetylation, in addition to the epigenetic regulation of oncogenic NF-κB and STAT3 signaling by resveratrol. Further, we evaluate the literature supporting the potentiation of HDAC inhibitors and the inhibition of DNMTs by resveratrol in different human cancers. This discussion underlines a robust epigenetic activity of resveratrol that warrants further evaluation, particularly in clinical settings.