Open Access Research article

Resistance to ursodeoxycholic acid-induced growth arrest can also result in resistance to deoxycholic acid-induced apoptosis and increased tumorgenicity

Ashley A Powell12, Sandeep Akare34, Wenqing Qi35, Pascal Herzer67, Samira Jean-Louis18, Rebecca A Feldman1 and Jesse D Martinez3*

Author Affiliations

1 Cancer Biology Interdisciplinary Program, University of Arizona, Arizona Cancer Center, Tucson, AZ, 85724, USA

2 Department of Surgery, Stanford University, MSLS P229, 1201 Welch Road, Stanford, CA 94305, USA

3 Department of Cell Biology and Anatomy, University of Arizona, Arizona Cancer Center, Tucson, AZ, 85724, USA

4 Department of Pathobiology, College of Veterinary Medicine University of Illinois Urbana Champagne, 2001 South Lincoln Avenue, Urbana, IL 61802, USA

5 Department of Medicine, University of Arizona, Arizona Cancer Center, Tucson, AZ, 85724, USA

6 Applied Biosciences Program, University of Arizona, Tucson, AZ 85724, USA

7 The Scripps Research Institute, Office of Technology Development, 10550 N. Torrey Pines Rd., La Jolla, CA 92037, USA

8 Department of Nutritional Sciences, University of Arizona, Tucson AZ 85724, USA

For all author emails, please log on.

BMC Cancer 2006, 6:219  doi:10.1186/1471-2407-6-219

Published: 1 September 2006



There is a large body of evidence which suggests that bile acids increase the risk of colon cancer and act as tumor promoters, however, the mechanism(s) of bile acids mediated tumorigenesis is not clear. Previously we showed that deoxycholic acid (DCA), a tumorogenic bile acid, and ursodeoxycholic acid (UDCA), a putative chemopreventive agent, exhibited distinct biological effects, yet appeared to act on some of the same signaling molecules. The present study was carried out to determine whether there is overlap in signaling pathways activated by tumorogenic bile acid DCA and chemopreventive bile acid UDCA.


To determine whether there was an overlap in activation of signaling pathways by DCA and UDCA, we mutagenized HCT116 cells and then isolated cell lines resistant to UDCA induced growth arrest. These lines were then tested for their response to DCA induced apoptosis.


We found that a majority of the cell lines resistant to UDCA-induced growth arrest were also resistant to DCA-induced apoptosis, implying an overlap in DCA and UDCA mediated signaling. Moreover, the cell lines which were the most resistant to DCA-induced apoptosis also exhibited a greater capacity for anchorage independent growth.


We conclude that UDCA and DCA have overlapping signaling activities and that disregulation of these pathways can lead to a more advanced neoplastic phenotype.