A Celecoxib Derivative Potently Inhibits Proliferation of Colon Adenocarcinoma Cells by Induction of Apoptosis

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.