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Published on: July 5, 2017
Epigenetic Effects of Blackberry Extract on Human Colorectal Cancer Cells
Mohsen Tatar1, Masoumeh Varedi2, Fakhraddin Naghibalhossaini1,3
1Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
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.
Insights
Blackberry extract impacts cancer epigenetics by altering DNA methyltransferases and histone deacetylases. This study reveals novel epigenetic effects of blackberry in colorectal cancer cells, influencing gene expression and cell differentiation.
Area of Science:
- Epigenetics
- Cancer Biology
- Nutraceuticals
Background:
- Polyphenolic compounds from fruits exhibit anticancer properties through epigenetic modifications.
- Epigenetic regulators like DNA methyltransferases (DNMTs) and histone deacetylases (HDACs) are crucial in cancer development.
- Colorectal cancer (CRC) presents a significant global health challenge, necessitating novel therapeutic strategies.
Purpose of the Study:
- To investigate the epigenetic effects of blackberry extract on DNMTs and HDACs in human CRC cell lines.
- To assess the impact of blackberry extract on cellular differentiation and tumor-related gene promoter DNA methylation.
- To establish blackberry as a potential agent for epigenetic cancer therapy.
Main Methods:
- Treatment of six human CRC cell lines with blackberry extract at IC20 and IC50 concentrations for 72 hours.
- Quantitative analysis of DNMTs (Dnmt1, Dnmt3a, Dnmt3b) and HDACs (HDAC1-4, SIRT1) gene expression.
- Assessment of promoter DNA methylation and expression of colonic epithelial cell differentiation markers (CEA, alkaline phosphatase).
Main Results:
- Blackberry extract significantly reduced Dnmt1 and Dnmt3b transcript levels in a dose-dependent manner across multiple CRC cell lines.
- Demethylation of SFRP2 and p16 gene promoters was observed, alongside cell-type-specific upregulation of Dnmt3a.
- Reduced expression of HDAC1, HDAC2, and HDAC4, and induced SIRT1 expression were noted, with increased CEA and alkaline phosphatase in LS180 cells.
Conclusions:
- Blackberry extract modulates key epigenetic enzymes (DNMTs and HDACs) in CRC cells.
- The study provides the first evidence of blackberry's epigenetic influence on cancer cells, affecting gene methylation and cellular differentiation.
- Blackberry extract demonstrates potential as a natural agent for epigenetic intervention in colorectal cancer.
