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Butyrate and deoxycholic acid play common and distinct roles in HCT116 human colon cell proliferation
Author(s) -
Zeng Huawei,
Claycombe Kate,
Reindl Katie
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.752.4
Subject(s) - butyrate , deoxycholic acid , apoptosis , cell cycle , cell growth , chemistry , wnt signaling pathway , sodium butyrate , biochemistry , bile acid , microbiology and biotechnology , cancer research , biology , signal transduction , fermentation , gene
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 butyrate increased intracellular reactive oxygen species (ROS), genomic DNA breakage, the activation of ERK1/2, caspase‐3 and PARP. In contrast, butyrate but not DCA increased p21 expression. Taken together, although both butyrate and DCA inhibit colonic cell proliferation, butyrate increases tumor suppressor gene expression, whereas DCA decreases tumor suppressor activation in cell cycle and apoptosis pathways.