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

Publisher: BioMed Central Country of Publication: England NLM ID: 100967800 Publication Model: Electronic Cited Medium: Internet ISSN: 1471-2407 (Electronic) Linking ISSN: 14712407 NLM ISO Abbreviation: BMC Cancer Subsets: MEDLINE

Original Publication: London : BioMed Central, [2001-

Drug Resistance, Neoplasm*/physiology; Apoptosis/*drug effects ; Cell Proliferation/*drug effects ; Deoxycholic Acid/*pharmacology ; Neoplasms/*prevention & control ; Ursodeoxycholic Acid/*pharmacology; Antineoplastic Agents/pharmacology ; Bile Acids and Salts/pharmacology ; Cell Adhesion/drug effects ; HCT116 Cells ; Humans ; Mutagenicity Tests ; Poly(ADP-ribose) Polymerases/metabolism

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.

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CA72008 United States CA NCI NIH HHS; P30 CA023074 United States CA NCI NIH HHS; T32CA09213 United States CA NCI NIH HHS; T32 CA009213 United States CA NCI NIH HHS; P01 CA072008 United States CA NCI NIH HHS

0 (Antineoplastic Agents)
0 (Bile Acids and Salts)
005990WHZZ (Deoxycholic Acid)
724L30Y2QR (Ursodeoxycholic Acid)
7A33Y6EHYK (hyodeoxycholic acid)
EC 2.4.2.30 (Poly(ADP-ribose) Polymerases)

Date Created: 20060905 Date Completed: 20061114 Latest Revision: 20181113

20231215

PMC1574338

10.1186/1471-2407-6-219

16948850