A celecoxib derivative potently inhibits proliferation of colon adenocarcinoma cells by induction of apoptosis.
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.[1]References
- A celecoxib derivative potently inhibits proliferation of colon adenocarcinoma cells by induction of apoptosis. Kusunoki, N., Ito, T., Sakurai, N., Handa, H., Kawai, S. Anticancer Res. (2006) [Pubmed]
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