Epigenetic Effects of Blackberry Extract on Human Colorectal Cancer Cells

Abstract

Fruit-derived polyphenolic compounds have been shown to exert anticancer effects <i>via</i> epigenetic mechanisms. In this study, we investigated the effect of blackberry extract on the expression of DNMTs (<i>Dnmt1</i>, <i>Dnmt3a</i>, and <i>Dnmt3b</i>) and HDACs (<i>HDAC1-4</i> and <i>SIRT1</i>) and its influence on the cellular differentiation and promoter DNA methylation of tumor-related genes using a panel of six human CRC cell lines. Treatment with IC₂₀ and IC₅₀ concentrations of blackberry extract for 72 h significantly reduced <i>Dnmt1</i> and <i>Dnmt3b</i> transcript levels in HCT116, SW480, HT29/219, SW742, and LS180 cells in a dose-dependent manner. Blackberry also induced promoter DNA demethylation of <i>SFRP2</i> and <i>p16</i> genes in four tested CRC cell lines. Berry treatment, however, upregulated <i>Dnmt3a</i> genes in SW480, SW742, and HT29/219 cell lines. A dose-dependent and cell-type-specific reduction of <i>HDAC1</i>, <i>HDAC2</i>, and <i>HDAC4</i> expressions were observed in CRC-treated cells. Treatment with berry extract induced the expression of <i>SIRT1</i> gene in HCT116 and HT29/219 cells and increased the expression of two colonic epithelial cell differentiation markers, carcinoembryonic antigen (CEA) and alkaline phosphatase in LS180 cells in a time-dependent manner. This study is the first to report the epigenetic effects of blackberry in cancer cells.