The role of histone acetylation in mediating the anticancer effects of polyphenols: Insights from genistein, resveratrol, quercetin, curcumin, and epigallocatechin-3-gallate.

Dysregulation of histone acetylation is a central epigenetic driver of oncogenesis. This review details the epigenetic modulating roles of five key dietary polyphenols-genistein (GEN), resveratrol (RES), quercetin (QUE), curcumin (CUR), and epigallocatechin-3-gallate (EGCG)-specifically focusing on their ability to modulate histone acetyltransferases (HATs) and inhibit histone deacetylases (HDACs). It elucidates the molecular mechanisms through which these compounds restore tumor suppressor gene expression, induce cell cycle arrest and apoptosis, and inhibit angiogenesis, metastasis, and drug resistance. Notably, CUR exhibits a distinct dual modulatory effect through its targeted inhibition of the p300/CBP HAT family, which effectively suppresses oncogenic transcription. Furthermore, this article examines the synergistic potential of combining these polyphenols with synthetic HDAC inhibitors and chemotherapy to enhance therapeutic efficacy while reducing associated toxicity. Finally, it addresses the major translational barriers, including limited bioavailability and rapid metabolic degradation, and evaluates emerging strategies such as structural optimization and nanotechnology-based delivery systems to facilitate the clinical application of polyphenol-based epigenetic therapies.