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

Ashley A. Powell, Sandeep Akare, Wenqing Qi, Pascal Herzer, Samira Jean-Louis, Rebecca A. Feldman, Jesse D Martinez

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

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

Original languageEnglish (US)
Article number219
JournalBMC Cancer
Volume6
DOIs
StatePublished - Sep 1 2006

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Ursodeoxycholic Acid
Deoxycholic Acid
Apoptosis
Bile Acids and Salts
Growth
Cell Line
HCT116 Cells
Carcinogens
Colonic Neoplasms
Carcinogenesis
Phenotype

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Resistance to ursodeoxycholic acid-induced growth arrest can also result in resistance to deoxycholic acid-induced apoptosis and increased tumorgenicity. / Powell, Ashley A.; Akare, Sandeep; Qi, Wenqing; Herzer, Pascal; Jean-Louis, Samira; Feldman, Rebecca A.; Martinez, Jesse D.

In: BMC Cancer, Vol. 6, 219, 01.09.2006.

Research output: Contribution to journalArticle

Powell, Ashley A. ; Akare, Sandeep ; Qi, Wenqing ; Herzer, Pascal ; Jean-Louis, Samira ; Feldman, Rebecca A. ; Martinez, Jesse D. / Resistance to ursodeoxycholic acid-induced growth arrest can also result in resistance to deoxycholic acid-induced apoptosis and increased tumorgenicity. In: BMC Cancer. 2006 ; Vol. 6.
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AU - Qi, Wenqing

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AU - Jean-Louis, Samira

AU - Feldman, Rebecca A.

AU - Martinez, Jesse D

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