Epigenetic Mechanisms of Quercetin and Other Flavonoids in Cancer Therapy and Prevention

Abstract Flavonoids are the most abundant polyphenols in fruits, vegetables, and plant-derived beverages, and their presence in food has been associated with many positive outcomes in terms of protection against overall mortality and degenerative diseases. Recent findings suggest that quercetin and other flavonoids may possess the capacity to counteract the adverse epigenetic regulation involved in various forms of cancer. Epigenetics is the study of heritable changes in gene expression independent from those occurring in the genome and includes histone modifications, DNA methylation, and posttranscriptional gene regulation by noncoding RNAs. In general, hypomethylation leads to activation of genes that cause cancer, whereas global DNA hypomethylation is common in the metastatic phase. In several cases, it has been shown that hypermethylation of tumor-suppressive genes determines the silencing of these genes that is commonly associated with cancer development. In recent years, several studies have demonstrated that dietary factors may influence the structure of chromatin and contribute to regulating both gene transcription and translation. Here, we review the role of quercetin and other flavonoids in regulating epigenetic processes in cancer cells. Being that a large part of the studies analyzed are based on preclinical models, we conclude that although promising, the impact of flavonoids in the regulation of key epigenetic mechanisms controlling cancer requires validation from clinical studies.