Microbial metabolite deoxycholic acid inhibits noncancerous NCM460 human colon cell proliferation: an inverse correlation between Bmal1:Clock gene expression and cell apoptosis

Dec 7, 2025Archives of biochemistry and biophysics

Deoxycholic acid from microbes may slow growth of noncancerous human colon cells, linked to changes in Bmal1:Clock gene expression and cell death.

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Abstract

DCA treatment at 0.3- and 0.4-mM inhibited cell proliferation by 19% and 29%, respectively.

High fat diets are associated with increased levels of deoxycholic acid (DCA) in the colon.
DCA induces apoptosis and enriches a resistant mutant colon cell subpopulation.
The Bmal1Clock complex may regulate the apoptosis induced by DCA in colon cells.
In DCA-treated cells, protein levels of Bmal1, Clock, and Wee1 decreased by ≥47%, while Rev-Erbα increased by ≥172%.
Differential expression of 42 genes in the Wnt signaling pathway was observed in response to DCA.
In cancerous colon tissues, mRNA levels of Bmal1 and Rev-Erbα decreased by (≥) 15% and Wee1 increased by 38% compared to normal tissues.

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High fat diets increase colonic deoxycholic acid (DCA) concentrations, which induce apoptosis, and subsequently enrich a compensatory DCA-resistant mutant colon cell subpopulation. While circadian Bmal1 and Clock genes are key regulators for cell proliferation, little is known about the relationship between DCA-induced apoptosis and circadian gene regulation in normal colon cells. In this study, we employed a noncancerous NCM460 human colon cell model to simulate the effect of DCA on cell proliferation in the colon and hypothesized that DCA-induced apoptosis is regulated by the Bmal1Clock complex in colon cells. Compared to the control cells, the treatment with DCA at 0.3- and 0.4-mM inhibited cell proliferation (via cell cycle arrest and apoptosis) by 19 % and 29 %, respectively. As the Bmal1Clock complex and Wnt signaling pathways are interlinked with apoptotic processes, we identified that 42 genes were differentially expressed in the Wnt signaling pathway; and there was a decrease (≥47 %) in Bmal1, Clock and Wee1 protein levels but an increase (≥172 %) in Rev-Erbα protein levels in DCA-treated cells compared to the control cells. At clinical levels, the mRNA levels of Bmal1 and Rev-Erbα were decreased by (≥) 15 % while Wee1 was increased by 38 % in cancerous colon tissues compared to normal ones. Collectively, DCA inhibits noncancerous NCM460 colon cell proliferation via cell cycle arrest and apoptosis accompanied with a drop of Bmal1Clock gene expression and altered Wnt signaling pathways. The Bmal1Clock regulatory network is relatively normal in the DCA-treated noncancerous NCM460 colon cells but not in colon cancer tissues.

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Microbial metabolite deoxycholic acid inhibits noncancerous NCM460 human colon cell proliferation: an inverse correlation between Bmal1:Clock gene expression and cell apoptosis

Abstract

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