Black raspberries attenuate colonic adenoma development in Apc Min mice: Relationship to hypomethylation of promoters and gene bodies. Food Front 2020 Sep;1(3):234-242
Date
09/25/2021Pubmed ID
34557678Pubmed Central ID
PMC8457619DOI
10.1002/fft2.45Scopus ID
2-s2.0-85098235761 (requires institutional sign-in at Scopus site) 7 CitationsAbstract
Recent studies have suggested that in addition to promoter region, DNA methylation in intragenic and intergenic regions also changes during physiological processes and disease. The current study showed that feeding of black raspberries (BRBs) to Apc Min mice suppressed colon and intestinal tumors. MBDCap-seq suggested that dietary BRBs hypomethylated promoter, intragenic, and intergenic regions. Annotation of those regions highlighted genes in pathways involved in immune regulation, inflammatory signaling, production of nitric oxide and reactive oxygen species, and progression of colorectal cancer. BRB phytochemicals (e.g., ellagic acid, anthocyanins, oligosaccharides) and their gut bacterial metabolites (e.g., urolithin, protocatechuic acid, short-chain fatty acids) inhibited DNMT1 and DNMT3B activities in a cell-free assay. Our results suggest that BRBs' hypomethylating activities result from the combined effects of multiple BRB phytochemicals and their gut bacterial metabolites. Because similar substances are found in many plant products, our results with BRBs might also apply to commonly consumed fruits and vegetables.