Abstract 2088: The effect of sorghum on epigenetic modifications in colon cancer

Abstract

Abstract Colorectal cancer is a major public health issue, accounting for nearly 150,000 cases annually. Because colorectal cancer is correlated with inflammation and oxidative cellular stress, it would be highly beneficial to exploit bioactive components in our diet that could potentially inhibit cancer promotion. Certain varieties of the dietary grain sorghum (S. bicolor) contain high amounts bioactive polyphenols, which may contribute to the prevention of colon cancer due to their antioxidant properties, anti-inflammatory, and anti-carcinogenesis effects, some of which may be mediated by epigenetic mechanisms. Tumor suppressor genes are often hyper-methylated in tumors. Therefore, DNA methylation and histone acetylation patterns may affect the expression of genes that play a role in the promotion or prevention of colon cancer. Our objective is to investigate how high-polyphenol sorghum varietals impact epigenetic mechanisms in human colon cancer cells, including quantitating global DNA methylation and histone acetylation. We treated HCT116 human colon cancer cells with high-polyphenol sorghum extracts or solvent control, or 5 µM epigallocatechin gallate as a positive control, as it's known to decrease DNA methylation. Total RNA, protein, and DNA were harvested after 24 and 48 hours. mRNA expression of DNA methyltransferases (DNMT) were quantitated with qPCR. Our preliminary results suggest that high polyphenol sorghum may decrease the mRNA expression of DNMT1, the key enzyme that upholds methylation patterns after DNA synthesis. Furthermore, mRNA expression of DNMT 3A, which is the enzyme responsible for de novo DNA methylation, also indicated a decrease. We further plan to assess protein expression and catalytic activity of DNMTs and histone acetyltransferases in addition to global DNA methylation and histone acetylation to investigate the impact of these high polyphenol sorghum varietals on relevant epigenetic mechanisms in both HCT116 and CACO-2 cells. Consumption of high-polyphenol sorghum as part of the human diet may lead to global or gene-specific hypo-methylation or hyper-acetylation, and this may be of importance in the prevention of colon cancer. Research supported by USDA ARS Kansas. Citation Format: Zeguela Kamagate, Dmitriy Smolensky, Petra Tsuji. The effect of sorghum on epigenetic modifications in colon cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2088.