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.


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.


CONCLUSIONS
A slight modification of celecoxib enhanced the pro-apoptotic effect on colon adenocarcinoma cells.
Kusunoki
Natsuko
N
Division of Rheumatology, Department of Internal Medicine, Toho University Omori Medical Center, 6-11-1 Omori-Nishi, Ota-Ku, Tokyo.
Ito
Takumi
T
Sakurai
Nobuyuki
N
Handa
Hiroshi
H
Kawai
Shinichi
S
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015232:Dinoprostone / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D019073:HT29 Cells / Q000187:drug effects; D006801:Humans; D011720:Pyrazoles / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*; D000096926:Benzenesulfonamides
D020169:Caspases; D015232:Dinoprostone; D011720:Pyrazoles; D013449:Sulfonamides; C504152:4-(5-(4-aminophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide; D000096926:Benzenesulfonamides; C504153:N-(2-aminoethyl)-4-(5-(4-tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide