A celecoxib derivative potently inhibits proliferation of colon adenocarcinoma cells by induction of apoptosis

Anticancer Res. 2006 Sep-Oct;26(5A):3229-36.

Abstract

Background: Celecoxib, a selective cyclooxygenase (COX)-2 inhibitor, has a pro-apoptotic effect on colon adenocarcinoma cells via COX-independent mechanisms.

Materials and methods: The pro-apoptotic effect of N-(2-Aminoethyl)-4-[5- (4-tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl] benzenesulfonamide (TT101), a new derivative of celecoxib, was investigated on the HT-29 and SW480 colon adenocarcinoma cells. Cell proliferation and viability were assessed by incorporation of 5-bromo-2'-deoxyuridine and by the 2-(4-Iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium monosodium salt assay, respectively. Apoptosis was detected by identifying DNA fragmentation. Production of prostaglandin E2 by the HT-29 cells was analyzed.

Results: TT101 inhibited the proliferation of HT-29 and SW480 cells by inducing apoptosis more potently than celecoxib in a concentration-dependent manner. The COX-2 inhibitory effect of TT101 was weaker than that of celecoxib.

Conclusion: A slight modification of celecoxib enhanced the pro-apoptotic effect on colon adenocarcinoma cells.

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / pathology
  • Apoptosis / drug effects*
  • Caspases / metabolism
  • Cell Proliferation / drug effects*
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / pathology
  • Dinoprostone / metabolism
  • Enzyme Activation / drug effects
  • HT29 Cells / drug effects
  • Humans
  • Pyrazoles / pharmacology*
  • Sulfonamides / pharmacology*

Substances

  • 4-(5-(4-aminophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide
  • N-(2-aminoethyl)-4-(5-(4-tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide
  • Pyrazoles
  • Sulfonamides
  • Caspases
  • Dinoprostone