Epigenetics has been redefined multiple times and today, it is generally accepted as “an academic discipline for the study of changes in gene function that are heritable after mitotic and/or meiotic division without any change in DNA sequence and/or changes in cell phenotype”. DNA methylation and histone modifications are one of the major mechanisms of epigenetic modifications. Vitamins and biofactors can modulate these epigenetic modifications. Vitamin B2, B6, B12, folate, and some biofactors such as betaine and choline regulate DNA methylation and histone methylation via synthesizing S-adenosyl-L-methionine that is the unique methyl donor for C5 position of cytosine base and lysine residues in histone tails. Vitamin C, Fe2+, and 2-oxoglutarate are cofactors for ten-eleven translocation methylcytosine dioxygenases that are important for oxidative demethylation of cytosine base and for jumonji domain-containing histone demethylases that remove methyl groups from lysine residues in histone tails. Vitamin B2 is also a cofactor for lysine-specific histone demethylase. Pantothenate is a cofactor for histone acetyltransferases and niacin is a cofactor for NAD+-dependent histone deacetylases. Vitamins A, D, and E and biotin are also cofactors to regulate epigenetic modification
Vitamin K is known to be a cofactor for gamma-glutamyl carboxylase and has recently been revealed to have a variety of biological activities, including agonist effects on nuclear receptors and protection of brain neurons from oxidative stress. Based on this background, studies on vitamin K derivatives have been conducted to create compounds with enhanced theses effects. In this paper, the derivatives focusing on the nuclear receptor SXR (steroid and xenobiotic receptor) and the differentiation of brain neural stem cells into neurons are mainly introduced.
Our research group has focused on the anticancer activity of tocotrienol (T3), one of the vitamin E analogues, and has reported that a new redox-inactive T3 derivative (6-O-carboxypropyl-α-tocotrienol; T3E) exerts an inhibitory effect on the survival of human malignant mesothelioma cells. In the study of this inhibitory mechanism by DNA microarray, T3E significantly increased the expression of dickkopf-1 (DKK1) gene , a Wnt antagonist. The DKK1 upregulation was assumed to be mediated by epigenetic alterations. T3E suppressed the expression of DNA methyltransferases (DNMTs) and histone deacetylases (HDACs) in malignant mesothelioma cells. DNMTs and HDACs are strongly related to cancer pathogenesis. Furthermore, methylation-specific PCR and chromatin immunoprecipitation were carried out to analyze the effects of T3E in the DKK1 promoter region. As a result, T3E decreased DNA methylation and increased histone acetylation in the DKK1 promoter region. Moreover, T3E increased histone H3 lysine 4 (H3K4) methylation activity, whereas T3E had no effect on histone H3K9 and H3K27.These findings suggest that T3E could be a useful candidate for malignant mesothelioma treatment. It has been thought that targeting the epigenetic induction of tumor suppressor genes leads to effective strategy for cancer treatment. In this review, we introduce our study with explaining epigenetics in cancer.