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Celecoxib and tauro-ursodeoxycholic acid co-treatment inhibits cell growth in familial adenomatous polyposis derived LT97 colon adenoma cells.

Abstract
Chemoprevention would be a desirable strategy to avoid duodenectomy in patients with familial adenomatous polyposis (FAP) suffering from duodenal adenomatosis. We investigated the in vitro effects on cell proliferation, apoptosis, and COX-2 expression of the potential chemopreventives celecoxib and tauro-ursodeoxycholic acid (UDCA). HT-29 colon cancer cells and LT97 colorectal micro-adenoma cells derived from a patient with FAP, were exposed to low dose celecoxib and UDCA alone or in combination with tauro-cholic acid (CA) and tauro-chenodeoxycholic acid (CDCA), mimicking bile of FAP patients treated with UDCA. In HT-29 cells, co-treatment with low dose celecoxib and UDCA resulted in a decreased cell growth (14-17%, p<0.01). A more pronounced decrease (23-27%, p<0.01) was observed in LT97 cells. Cell growth of HT-29 cells exposed to 'artificial bile' enriched with UDCA, was decreased (p<0.001), either in the absence or presence of celecoxib. In LT97 cells incubated with 'artificial bile' enriched with UDCA, cell growth was decreased only in the presence of celecoxib (p<0.05). No clear evidence was found for involvement of proliferating cell nuclear antigen, caspase-3, or COX-2 in the cellular processes leading to the observed changes in cell growth. In conclusion, co-treatment with low dose celecoxib and UDCA has growth inhibitory effects on colorectal adenoma cells derived from a patient with FAP, and further research on this combination as promising chemopreventive strategy is desired.
AuthorsBjorn W H van Heumen, Hennie M J Roelofs, René H M Te Morsche, Brigitte Marian, Fokko M Nagengast, Wilbert H M Peters
JournalExperimental cell research (Exp Cell Res) Vol. 318 Issue 7 Pg. 819-27 (Apr 15 2012) ISSN: 1090-2422 [Electronic] United States
PMID22366264 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2012 Elsevier Inc. All rights reserved.
Chemical References
  • Cholagogues and Choleretics
  • Cyclooxygenase 2 Inhibitors
  • Pyrazoles
  • Sulfonamides
  • Taurochenodeoxycholic Acid
  • ursodoxicoltaurine
  • Celecoxib
Topics
  • Adenoma (drug therapy)
  • Adenomatous Polyposis Coli (drug therapy)
  • Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
  • Apoptosis (drug effects)
  • Celecoxib
  • Cell Line, Tumor
  • Cell Proliferation (drug effects)
  • Cholagogues and Choleretics (pharmacology)
  • Colonic Neoplasms (drug therapy)
  • Cyclooxygenase 2 Inhibitors (pharmacology)
  • HT29 Cells
  • Humans
  • Pyrazoles (pharmacology)
  • Sulfonamides (pharmacology)
  • Taurochenodeoxycholic Acid (pharmacology)

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