The Effect of Sorghum Polyphenols on DNA Methylation and Histone Acetylation in Colon Cancer

Abstract

Abstract Objectives Colorectal cancer (CRC) is a major public health issue, accounting for nearly 150,000 cases annually. Because CRC correlates with oxidative stress, exploiting the antioxidative nature of bioactive components in our diet that could potentially inhibit cancer promotion might be beneficial. New varietals of the grain Sorghum bicolor contain high amounts of polyphenols, which may contribute to CRC prevention due to their strong antioxidative and anti-carcinogenic properties. Because gene expression of enzymes may be mediated by epigenetic mechanisms, we are interested in DNA methylation and histone acetylation patterns of genes, including those enzymes that play a role in the promotion or prevention of CRC. Our objective is to examine how high-polyphenol sorghum varietals impact epigenetic mechanisms in human colon cancer cells. Methods We are currently assessing mRNA and protein expression, catalytic activity of DNA-methyltransferases (DNMTs) and histone acetyltransferases, in addition to global DNA methylation and histone acetylation in human HCT116 and CACO-2 colon cancer cells. We treated HCT116 cells with new high-polyphenol or commercially available S. bicolor extracts, solvent control, or 5 μM epigallocatechin gallate as a positive control for up to 48 hours. Total RNA, protein, and DNA were harvested, and mRNA expression of selected genes was quantitated with qPCR, and protein expression is being quantitated with Western blotting. Results Our preliminary results suggest that high-polyphenol S. bicolor may decrease mRNA expression of DNMT1, the key enzyme that upholds methylation patterns after DNA synthesis. Furthermore, mRNA expression of DNMT3A, the enzyme responsible for de novo DNA methylation, was also decreased. We will further investigate global and gene-specific DNA methylation, and the expression of genes involved in tumorigenesis and chemoprevention. Conclusions Consumption of high-polyphenol S. bicolor as part of the human diet may lead to beneficial changes in chromatin methylation or acetylation. Subsequently, the expression of specific genes involved in the promotion or prevention of colorectal cancer may be modified, providing a dietary intervention to CRC. Funding Sources Towson University. Bridges-to-Doctorate grant. USDA ARS Kansas.