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. 2010 Aug;26(4):254-9.
doi: 10.3393/jksc.2010.26.4.254. Epub 2010 Aug 31.

Effects of DCA on Cell Cycle Proteins in Colonocytes

Yun-Hyung Ha  1 , Dong-Guk Park
Affiliations

Effects of DCA on Cell Cycle Proteins in Colonocytes

Yun-Hyung Ha et al. J Korean Soc Coloproctol. 2010 Aug.

Abstract

Purpose: Evidence that indicates bile acid is a promoter of colon cancer exists. Deoxycholic acid (DCA) modifies apoptosis or proliferation by affecting intracellular signaling and gene expression. However, because previous studies have been based on studies on colon cancer cell lines, the effect of DCA on normal colonocytes is unknown.

Methods: Normal colonocytes and Caco-2 and HCT116 cells were treated with 20 µM and 250 µM of DCA, and the effect of different concentrations of DCA was measured based on the expression of cell-cycle-related proteins by using Western blots.

Results: The expressions of CDK2 and cyclin D1 for different concentrations of DCA in normal colonocytes and colon cancer cells were similar, but the expressions of cyclin E and A were significantly different. In HCT116 colon cancer cells, the expression of cyclin E increased regardless of the DCA concentration, but in normal colonocytes and Caco-2 cells, the expression of cyclin E was not changed or decreased. In HCT116 colon cancer cells, the expression of cyclin A was not changed or decreased regardless of the DCA concentration, but in normal colonocytes and Caco-2 cells, the expression of cyclin A was increased at a DCA concentration of 20 µM.

Conclusion: The effect of DCA on stimulating cell proliferation suggests that DNA synthesis is stimulated by an increased expression of cyclin E in colon cancer cells. Our results suggest that a low dose of DCA induces cellular proliferation through increased expression of cyclin A and that a high dose of DCA induces decreased expression of cyclin E and CDK2 in normal colonocytes.

Keywords: CDK2; Cell cycle; Colonocyte; Cyclin; Deoxycholic acid.

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Conflict of interest statement

No potential conflict of interest relevant to this article was reported.

Figures

Fig. 1
Fig. 1
Isolated human colonic crypt (A) and colonocytes (B). Human normal colonocytes were incubated for 24 hours with various concentration of deoxycholic acid: 0 (C), 20 µM (D), and 250 µM (E).
Fig. 2
Fig. 2
Change of cell-cycle-related proteins in human colonocytes after incubation for 24 hours with deoxycholic acid based on a Western blot analysis. Conc., concentration; ERK, extracellular signal-regulated kinase.
Fig. 3
Fig. 3
Comparison of the change in cell-cycle-related proteins in the Caco-2 colorectal cancer cell-line after incubation for 72 hours with deoxycholic acid based on a Western blot analysis. Conc., concentration; ERK, extracellular signal-regulated kinase.
Fig. 4
Fig. 4
Comparison of the change in the cyclin E protein in human colonocytes and in HCT116 colon cancer cells after incubation for 24 hours with deoxycholic acid based on a Western blot analysis. ERK, extracellular signal-regulated kinase.
Fig. 5
Fig. 5
Comparison of the change of Cdk2 protein after incubation for 24 hours with deoxycholic acid in human colonocytes and HCT116 colon cancer cells by Western blot analysis. ERK, extracellular signal-regulated kinase.
Fig. 6
Fig. 6
Comparison of the change in the cyclin A protein in human colonocytes and HCT116 colon cancer cells after incubation for 24 hours with deoxycholic acid based on a Western blot analysis. ERK, extracellular signal-regulated kinase.
Fig. 7
Fig. 7
Comparison of the change in the cyclin D1 protein in human colonocytes and HCT116 colon cancer cells after incubation for 24 hours with deoxycholic acid based on a Western blot analysis. ERK, extracellular signal-regulated kinase.
See this image and copyright information in PMC

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