Microbially mediated phenolic catabolites exert differential genoprotective activities in normal and adenocarcinoma cell lines

Age-associated decline of nuclear factor erythroid 2-related factor 2 (Nrf2) activity and DNA repair efficiency leads to the accumulation of DNA damage and increased risk of cancer. Understanding the mechanisms behind increased levels of damaged DNA is crucial for developing interventions to mitigate age-related cancer risk. Associated with various health benefits, (poly)phenols and their microbially mediated phenolic catabolites represent a potential means to reduce DNA damage. Four colonic-microbiota-derived phenolic catabolites were investigated for their ability to reduce H₂O₂-induced oxidative DNA damage and modulate the Nrf2-Antixoidant Response Element (ARE) pathway, in normal (CCD 841 CoN) and adenocarcinoma (HT29) colonocyte cell lines. Each catabolite demonstrated significant (p < .001) genoprotective activity and modulation of key genes in the Nrf2-ARE pathway. Overall, the colon-derived phenolic metabolites, when assessed at physiologically relevant concentrations, reduced DNA damage in both normal and adenocarcinoma colonic cells in response to oxidative challenge, mediated in part via upregulation of the Nrf2-ARE pathway.