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Abstract
Fruit-derived polyphenolic compounds have been shown to exert anticancer effects via epigenetic mechanisms. In this study, we investigated the effect of blackberry extract on the expression of DNMTs (Dnmt1, Dnmt3a, and Dnmt3b) and HDACs (HDAC1-4 and SIRT1) 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 Dnmt1 and Dnmt3b transcript levels in HCT116, SW480, HT29/219, SW742, and LS180 cells in a dose-dependent manner. Blackberry also induced promoter DNA demethylation of SFRP2 and p16 genes in four tested CRC cell lines. Berry treatment, however, upregulated Dnmt3a genes in SW480, SW742, and HT29/219 cell lines. A dose-dependent and cell-type-specific reduction of HDAC1, HDAC2, and HDAC4 expressions were observed in CRC-treated cells. Treatment with berry extract induced the expression of SIRT1 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.
Acknowledgments
This research was a part of the dissertation of Mohsen Tatar submitted to Shiraz University of Medical Sciences in partial fulfillment of the requirements for the Ph.D. in clinical biochemistry.
Disclosure Statement
The authors have no competing interests.
MT performed all experiments and acquisition of data. MV assisted in the supervision of the research. FN conceived and designed the experiments and prepared the manuscript. All authors read and approved the final form of the submitted manuscript.
Funding
This work was supported by the Vice-Chancellor for Research, Shiraz University of Medical Sciences through Grant Number 94-010110457.