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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 #312642
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 Nutritional Biochemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/14/2015
Publication Date: 10/1/2015
Publication URL: http://handle.nal.usda.gov/10113/61624
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. Journal of Nutritional Biochemistry. 26:1022-1028.

Interpretive Summary: Colon cancer accounts for approximately 140,000 new cancer cases and 50,000 deaths each year in the US, and it is predicted that half the Western population will develop at least one colorectal tumor by the age of 70 years. 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. The aim of this study is to distinguish these opposing effects of DCA and butyrate (two major metabolites in colon lumen). In this study, we found that both butyrate and DCA, inhibited colon cancer cell proliferation by up to 89% and 92% after 72 h treatment, respectively. Although butyrate and DCA inhibit colonic cell proliferation, butyrate increases tumor suppressor gene expression, whereas DCA decreases the activation of tumor suppressor in cell cycle and apoptosis pathways. These observations may, in part, provide the mechanistic explanation that high fiber consumption reduces colon cancer risk (due to high dietary fat intake). The information will be useful for scientists and health-care professionals who are interested in dietary fat, fiber and colon cancer prevention.

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 (0.5 - 2 mol/L) and DCA (0.05 - 0.3 mol/L) 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. In this study, we demonstrated that, both butyrate and DCA, inhibited colon cancer cell proliferation by up to 89% and 92% and; increased cell apoptosis rate by up to 40% and 58% 72 h treatment, 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 when compared with the untreated cells. The examination of early cellular signaling revealed that DCA but not butyrate increased intracellular reactive oxygen species (ROS), genomic DNA breakage, the activation of ERK1/2, caspase-3 and PARP. In contrast, DCA decreased activated-Rb protein level, and 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 the activation of tumor suppressor in cell cycle and apoptosis pathways.