Gene expression, cell cycle arrest and MAPK signalling regulation in Caco-2 cells exposed to ellagic acid and its metabolites, urolithins.

Novel gene expression profiles and cellular functions modulated in Caco-2 cells in response to the dietary polyphenol, ellagic acid (EA), and its colonic metabolites, urolithin-A (3,8-dihydroxy-6H-dibenzo[b,d] pyran-6-one) and urolithin-B (3-hydroxy-6H-dibenzo[b,d] pyran-6-one) have been identified. Exposure of cells to EA and urolithins arrested cell growth at the S- and G(2)/M-phases. Transcriptional profiling using microarray and functional analysis revealed changes in the expression levels of MAPK signalling genes such as, growth factor receptors (FGFR2, EGFR), oncogenes (K-Ras, c-Myc), and tumour suppressors (DUSP6, Fos) and of genes involved in cell cycle (CCNB1, CCNB1IP1). Results suggest that EA and urolithin-A and -B, at concentrations achievable in the lumen from the diet, might contribute to colon cancer prevention by modulating the expression of multiple genes in epithelial cells lining the colon. Some of these genes are involved in key cellular processes associated with cancer development and are currently being investigated as potential chemopreventive targets.