Dietary Phytochemicals As Epigenetic Modifiers In Cancer: Current Challenges And Prospect
OKOROAMA EMEKA CASMIR* AND UNEKWE PRINCE CHIAZO
Department of Pharmacology and Therapeutics, Faculty of Medicine, college of Health Sciences, Nnamdi Azikiwe University, Nnewi Campus, Anambra State, Nigeria.
Afr. J Pharm Res Dev; Volume 12(2): 134-151 ; 2020
Diet and environment play important role in human health. Most plant-derived natural bioactive compounds (phytochemicals) in our diets are potent antioxidants and cancer chemo-preventive agents. Dietary phytochemicals (Sulforaphane, catechins/epicatechins, Genistein, Resveratrol, Lycopene, and others) have been found to play significant role as epigenetic modifiers in several cancers. Epigenetics was first defined as the complex interplay between the genome and environmental factors that govern cell differentiation and development. At the current time, this term refers to heritable traits that are not a consequence of changes in DNA sequence, rather the result of alterations in gene expression regulated by changes in DNA accessibility or chromatin structure. Epigenetic modifications can be affected by exogenous factors providing a link between genes (or the genome) and environment (or the exposome) in defining phenotype variations. The field of epigenetics is expanding rapidly, with a number of ongoing international research initiatives, including the Human Epigenome Project and the International Human Epigenome Consortium. In past few decades, the role of epigenetic alterations such as DNA methylation, histone modifications and non-coding RNAs in the regulation of mammalian genome had been comprehensively addressed. Defining the determinants of epigenetic regulation offers opportunities for novel strategies for disease prevention and treatment. Several epigenetically active synthetic molecules such as DNA methyltransferases (DNMTs) and histone deacetylases (HDACs) inhibitors, are either approved or, under clinical trials for the treatment of various cancers. However, most of the synthetic inhibitors have shown adverse side effects, narrow therapeutic index and are expensive. Hence, bioactive phytochemicals, which are widely available with lesser toxic effects, have been tested for their role in epigenetic modulatory activities in gene regulation for cancer prevention and therapy. These bioactive phytochemicals showed promising results against various cancers. This review discusses the role of commonly investigated phytochemicals and their epigenetic targets that are of particular interest in cancer prevention and therapy; as well as the progress in cancer chemoprevention with dietary phytochemicals.
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KEYWORDS: Phytochemicals, Epigenetics, DNA methylation, histone modifications, non-coding RNAs.