Epigenetics of Dietary Phytochemicals in Cancer Prevention: Fact or Fiction.

Abstract: Cancer development takes 10 to 50 years, and epigenetics plays an important role. Recent evidence suggests that ~80% of human cancers are linked to environmental factors impinging upon genetics/epigenetics. Because advanced metastasized cancers are resistant to radiation/chemotherapeutic drugs, cancer prevention by relatively nontoxic "epigenetic modifiers" will be logical. Many dietary phytochemicals possess powerful antioxidant and anti-inflammatory properties that are hallmarks of cancer prevention. Dietary phytochemicals can regulate gene expression of the cellular genome via epigenetic mechanisms. In this review, we will summarize preclinical studies that demonstrate epigenetic mechanisms of dietary phytochemicals in skin, colorectal, and prostate cancer prevention. Key examples of the importance of epigenetic regulation in carcinogenesis include hypermethylation of the NRF2 promoter region in cancer cells, resulting in inhibition of NRF2-ARE signaling. Many dietary phytochemicals demethylate NRF2 promoter region and restore NRF2 signaling. Phytochemicals can also inhibit inflammatory responses via hypermethylation of inflammation-relevant genes to block gene expression. Altogether, dietary phytochemicals are excellent candidates for cancer prevention due to their low toxicity, potent antioxidant and anti-inflammatory properties, and powerful epigenetic effects in reversing procarcinogenic events.
Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. This work was supported in part by institutional funds and by R01 AT009152 from the National Center for Complementary and Integrative Health, R01 CA200129 from the National Cancer Institute, and P30 ES005022 from the National Institute of Environmental Health.
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