Butyrate Inhibits Deoxycholic‐Acid‐Resistant Colonic Cell Proliferation via Cell Cycle Arrest and Apoptosis: A Potential Pathway Linking Dietary Fiber to Cancer Prevention

Scope Butyrate, an intestinal microbiota metabolite of dietary fiber, exhibits colon cancer preventive effects. In contrast, a high fat intake increases fecal secondary bile acids, such as deoxycholic acid (DCA, a potential cancer promoter), which selectively enrich mutant epithelial cells with an abnormally high resistance to DCA‐induced apoptosis in the colon. This study is conducted to test the hypothesis that physiological concentrations of butyrate inhibit DCA‐resistant colonic cell proliferation. Methods and results With human HCT‐116 cells as parental colonic cells, a human DCA‐resistant colonic cell line (DCA‐RCL) is developed. DCA treatment increases apoptosis and intracellular reactive oxygen species (an apoptotic trigger) at a rate threefold greater in HCT‐116 cells than in DCA‐RCL cells. Subsequently, 41 apoptosis related genes (including signaling pathways) with greater than onefold (mRNA) change in DCA‐RCL cells are identified compared with HCT‐116 cells. Moreover, butyrate treatment inhibits DCA‐RCL cell proliferation with similar efficacy when compared with HCT116 cells via cellular myelocytomatosis oncogene (c‐Myc)/p38 mitogen‐activated protein kinase pathway. Conclusion It is demonstrated that butyrate inhibits DCA‐RCL cell proliferation at the cellular and molecular level. These data provide a proof of concept that butyrate can protect against colon carcinogenesis through a specific targeting of DCA‐resistant colonic cells.