[Mechanism of apoptosis induced by specific COX-2 inhibitor SC236 in gastric cancer cells].
OBJECTIVE
To investigate the underlying mechanism of apoptosis-inducing effect of a specific COX-2 inhibitor SC236 in gastric cancer cells.


METHODS
Western blot analysis was used to measure apoptosis-related proteins, cytochrome c, and caspase-3. The catalytic activity of the caspases was measured using a colorimetric assay.


RESULTS
Treatment of AGS gastric cancer cells with SC236 caused a significant elevation of the pro-apoptotic protein Bak, release of cytochrome c to the cytosol, and activation of caspase-3. A specific caspase-3 inhibitor, z-DEVD-fmk, blocked SC236-induced apoptosis.


CONCLUSIONS
SC236 inhibits cell growth and induces apoptosis in gastric cancer cells at least partly through the up-regulation of Bak, stimulation of cytochrome c release, and activation of caspase-3.
Fan
Xiao-ming
XM
Department of Medicine, Jinshan Hospital of Fudan University, Shanghai 200540, China. xiaomingfan57@sina.com
Zheng
Fa-shou
FS
Liu
Hong-yan
HY
Ma
Yuan-hua
YH
Wong
B C Y
BC
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D045304:Cytochromes c / Q000378:metabolism; D006801:Humans; D009842:Oligopeptides / Q000494:pharmacology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology*; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology*; D013449:Sulfonamides / Q000494:pharmacology*; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000378:metabolism*; D000096926:Benzenesulfonamides
D053148:Caspase 3; D020169:Caspases; D052246:Cyclooxygenase 2 Inhibitors; D045304:Cytochromes c; D009842:Oligopeptides; D011065:Poly(ADP-ribose) Polymerases; D011720:Pyrazoles; D013449:Sulfonamides; D050998:bcl-2 Homologous Antagonist-Killer Protein; C119130:4-(5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide; D000096926:Benzenesulfonamides; C110772:benzoylcarbonyl-aspartyl-glutamyl-valyl-aspartyl-fluoromethyl ketone; C505407:CASP3 protein, human