Effect of bile acids on butyrate-sensitive and -resistant human colon adenocarcinoma cells
2005
Perez-Ramos, P. | Olmo, N. | Turnay, J. | Lecona, E. | Gonzalez de Buitrago, G. | Portoles, M.T. | Lizarbe, M.A.
A controlled balance among cell proliferation, differentiation, and apoptosis is required for the maintenance of gastrointestinal mucosa; these processes are influenced by luminal components, such as butyrate and bile acids. Using butyrate-sensitive (BCS-TC2) and butyrate-resistant (BCS-TC2.BR2) human colon carcinoma cells, we wanted to establish whether colon carcinoma cells that acquire resistance to butyrate-induced apoptosis are also resistant to the cytotoxic effect of certain bile acids, contributing, in this way, to the progression of colon carcinogenesis. The effect of bile acids on BCS-TC2 cell viability is dose and time dependent and highly stereospecific. Quantification of the relative percentage of apoptotic cells and caspase-3 activity reveals that deoxycholic acid (DCA) and chenodeoxycholic acid (CDCA) induce apoptosis in BCS-TC2 cells. BCS-TC2.BR2 cells are consistently less sensitive to their cytotoxic effects, requiring concentrations to induce 50% inhibition (IC50) in cell viability of 740 micromolar and >1 mM for CDCA and DCA, respectively, compared with IC50 values of 310 and 540 micromolar for BCS-TC2 cells. DCA-treated BCS-TC2.BR2 cells show few apoptotic signs and no caspase-3 activation. On the other hand, CDCA-treated BCS-TC2.BR2 cells show caspase-3 activation and apoptotic features, although to a lower extent than BCS-TC2 cells. Our results, in an in vitro model system, point out that acquisition of butyrate resistance is accompanied by a partial resistance to the cytotoxic effects of bile acids, which may enhance the survival of tumorigenic cells.
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