Abstract
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.
