Epi-nutrients for cancer prevention: Molecular mechanisms and emerging insights

The burgeoning field of epigenetics holds considerable potential in cancer prevention and management, as it targets mechanisms essential to regulating gene expression without altering DNA sequences. Epigenetic processes like DNA methylation, histone modifications, non-coding RNAs, and nucleosome remodelling-play an essential role in cellular differentiation and development, with dysfunction in these pathways often leading to malignancy. Targeting epigenetic regulators, including DNA methyltransferases (DNMTs) and histone deacetylases (HDACs), can suppress cancer cell proliferation, making epigenetics a promising therapeutic frontier. Phytochemicals, natural bioactive compounds predominantly found in vegetables, fruits, and seeds, offer a complementary approach to traditional cancer therapies through their epigenetic influence. These compounds exhibit anti-inflammatory, anti-angiogenic, and antioxidant properties, which modulate pathways and proteins involved in chromatin remodeling and may influence the mammalian epigenome. A diverse spectrum of bioactive dietary ingredients, including curcumin, epigallocatechin-3-gallate (EGCG), genistein, quercetin, resveratrol, and sulforaphane, has gained significant interest for their ability to modulate gene expression and chromatin structure via epigenetic mechanisms. Their potential implications for cancer prevention and their role in regulating key epigenetic genes have been described in numerous investigations. This comprehensive review explores the molecular mechanisms by which dietary bioactive molecules may reverse epigenetic aberrations in cancer cells. It examines the influence of these compounds on DNA methylation, ten-eleven translocation (TET) enzymes, and histone modifications, while discussing their specific molecular targets in various cancer types. Additionally, we highlight the pathways through which these epi-nutrients may impact gene expression and enzyme activities associated with epigenetic regulation, which leads to innovative, diet-based anticancer strategies. Clinical trial number: not applicable.