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Selective cyclooxygenase‐2 inhibitors show a differential ability to inhibit proliferation and induce apoptosis of colon adenocarcinoma cells
Author(s) -
Yamazaki Ryuta,
Kusunoki Natsuko,
Matsuzaki Takeshi,
Hashimoto Shusuke,
Kawai Shinichi
Publication year - 2002
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(02)03535-4
Subject(s) - celecoxib , apoptosis , rofecoxib , cyclooxygenase , meloxicam , dna fragmentation , cancer research , fragmentation (computing) , cell growth , adenocarcinoma , prostaglandin e2 , chemistry , cell culture , tunel assay , nimesulide , cox 2 inhibitor , pharmacology , programmed cell death , biology , medicine , enzyme , biochemistry , cancer , ecology , genetics
Although the influence of selective cyclooxygenase (COX)‐2 inhibitors on the proliferation of colon adenocarcinoma cells have been the subject of much investigation, relatively little research has compared the effects of different COX‐2 inhibitors. Celecoxib strongly suppressed the proliferation of COX‐2 expressing HT‐29 cells at 10–40 μM. NS‐398 and nimesulide also inhibited cell proliferation, whereas rofecoxib, meloxicam, and etodolac did not. Only celecoxib induced apoptosis of HT‐29 cells, as detected on the basis of DNA fragmentation, TUNEL positivity, and caspase‐3/7 activation. DNA fragmentation was also increasd in COX‐2 non‐expressing cell lines (SW‐480 and HCT‐116) by exposure to celecoxib for 6–24 h. All six COX‐2 inhibitors suppressed the production of prostaglandin E 2 by HT‐29 cells, suggesting that the pro‐apoptotic effect of celecoxib was unrelated to inhibition of COX‐2. Inactivation of Akt might explain the differential pro‐apoptotic effect of these selective COX‐2 inhibitors on colon adenocarcinoma cells.