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

Author:
Huawei Zeng, Kate J. Claycombe, Katie M. Reindl
Source:
Journal of nutritional biochemistry 2015 v.26 no.10 pp. 1022-1028
ISSN:
0955-2863
Subject:
DNA, DNA damage, apoptosis, butyric acid, caspase-3, cell communication, cell cycle, cell proliferation, colon, colorectal neoplasms, deoxycholic acid, dietary fiber, gene expression, high fat diet, humans, intestinal microorganisms, metabolites, reactive oxygen species, tumor suppressor genes
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 mmol/l) and DCA (0.05–0.3 mmol/l) on colon 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 cell proliferation by up to 89% and 92% and increased cell apoptosis rate by up to 3.1- and 4.5-fold, 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 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, 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. Collectively, 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.
Agid:
61624
Handle:
10113/61624