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ARS Home » Plains Area » Grand Forks, North Dakota » Grand Forks Human Nutrition Research Center » Dietary Prevention of Obesity-related Disease Research » Research » Publications at this Location » Publication #311545
Title: Butyrate and deoxycholic acid play common and distinct roles in HCT116 human colon cell proliferation

Author
item Zeng, Huawei
item Larson, Kate
item REINDL, KATIE - North Dakota State University

Submitted to: Journal of Federation of American Societies for Experimental Biology
Publication Type: Abstract Only
Publication Acceptance Date: 1/15/2015
Publication Date: 3/28/2015
Citation: Zeng, H., Claycombe, K.J., Reindl, K.M. 2015. Butyrate and deoxycholic acid play common and distinct roles in HCT116 human colon cell proliferation [abstract]. Journal of Federation of American Societies for Experimental Biology. 29:752.4.

Interpretive Summary:

Technical 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. 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.