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Symposium: Diet Induced Changes in the Colonic Environment and Colorectal Cancer

Ursodeoxycholic Acid (UDCA) Can Inhibit Deoxycholic Acid (DCA)-induced Apoptosis via Modulation of EGFR/Raf-1/ERK Signaling in Human Colon Cancer Cells^1,2

Arizona Cancer Center, Department of Radiation Oncology, University of Arizona, Tucson, AZ 85724

³To whom correspondence should be addressed. E-mail: jmartinez{at}azcc.arizona.edu.

Ursodeoxycholic acid (UDCA), a hydrophilic bile acid, is known as a cytoprotective agent. UDCA prevents apoptosis induced by a variety of stress stimuli including cytotoxic bile acids such as deoxycholic acid (DCA). Here we examined the molecular mechanism by which UDCA can antagonize DCA-induced apoptosis in human colon cancer cells. UDCA pretreatment decreases the number of apoptotic cells caused by exposure to DCA and UDCA. Further studies of the signaling pathway showed that UDCA pretreatment suppressed DNA binding activity of activator protein-1 and this was accompanied by downregulation of both extracellular signal-regulated kinase (ERK) and Raf-1 kinase activities stimulated by exposure to DCA. DCA was also found to activate epidermal growth factor receptor (EGFR) activity and UDCA inhibited this. Collectively, these findings suggest that the inhibitory effect of UDCA in DCA-induced apoptosis is partly mediated by modulation of EGFR/Raf-1/ERK signaling.

KEY WORDS: • apoptosis • colon cancer • deoxycholic acid • ursodeoxycholic acid

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