Butyrate and deoxycholic acid play common and distinct roles in HCT116 human colon cell proliferation

Abstract

Consumption of a high fat diet causes an increase in bile acid deoxycholic acid (DCA) in colon lumen and colon cancer risk while butyrate, an intestinal microbiota metabolite of dietary fiber, has been shown to exhibit colon cancer preventive effects. To distinguish these opposing effects of DCA and butyrate (two major metabolites in colon lumen), we examined the effects of physiologically relevant doses of butyrate and DCA on colon cancer cell proliferation. We hypothesize that butyrate and DCA, each modulates the cell cycle and apoptosis via common and distinct cellular signaling targets. Both butyrate and DCA, inhibited colon cancer cell proliferation and; increased cell apoptosis rate, respectively; cell cycle analyses revealed that butyrate led to an increase in G1 and G2 fractions with a concomitant drop in the S-phase fraction, but DCA induced an increase in only the G1 fraction with a concomitant drop in the S-phase fraction. DCA decreased activated Rb protein level. Furthermore, DCA but not butyr...