Bile acids mimic oxidative stress induced upregulation of thioredoxin reductase in colon cancer cell lines

Abstract

Bile acids have been suggested to play an important role in the etiology of colon and gastric cancer after gastrectomy, but the molecular biology of these effects is poorly understood. We evaluated the effect of different bile acids on human gastric and colon carcinoma cells and identified genes by RNA arbitrarily primed PCR for differential display that are modulated following treatment with hydrophobic bile acids. Thioredoxin reductase (TR) mRNA was upregulated after treatment with taurochenodeoxycholic acid (TCDCA) in St 23132 cells. This raised the question whether deoxycholic acid (DCA) would have regulative effects on TR in HT-29 cells. After an incubation time of 6 h with DCA, TR mRNA expression was increased up to threefold. Ursodeoxycholic acid had no influence on TR mRNA expression. The upregulation of TR after DCA incubation was almost identical to incubation with 12-O-tetradecanoylphorbol-13-acetate. This implies that hydrophobic bile acids mediate oxidative stress in gastrointestinal cancer cells, which was confirmed by measurement of oxidative burst after treatment with DCA. The results suggest that hydrophobic bile acids induce oxidative stress in gastrointestinal cancer resulting in a compensatory upregulation of TR mRNA, one of the key components in the complex anti-oxidant defense system within eukaryotic cells. The activation of at least parts of the redox signaling system is potentially related to the cytotoxicity and the stimulation of the cell death machinery induced by toxic bile acids.