Open AccessApoptosis Induced by NS‐398, a Selective Cyclooxygenase‐2 Inhibitor, in Human Colorectal Cancer Cell Lines
Author(s) -
Kara Akira,
Yoshimi Naoki,
Niwa Masayuki,
Ino Natsuko,
Mori Hideki
Publication year - 1997
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.1997.tb00424.x
Subject(s) - apoptosis , cyclooxygenase , colorectal cancer , ic50 , enzyme inhibitor , cell culture , pharmacology , cancer , chemistry , medicine , endocrinology , biology , in vitro , enzyme , biochemistry , genetics
Recent studies have suggested that apoptosis is a key phenomenon in the chemopreventive action of nonsteroidal antiinflammatory drugs (NSAIDs), which exhibit cancer‐preventive and tumor‐regressive effects in the human colon. The effect of NS‐398, N ‐(2‐cyclohexyloxy‐4‐nitrophenyl)methanesul‐fonamide, which is a selective inhibitor of cyclooxygenase‐2 (COX‐2), on the induction of apoptosis in two human colorectal cancer cell lines (Colo320 and THRC) was determined. The apoptotic ratios (‐fold vs. control value) of Colo320 in the presence of 100 μM indomethacin and NS‐398 were 3.3 ± 1.5 and 9.0±0.94, and those of THRC were 2.3±0.46 and 7.4±0.87, respectively. The ability of NS‐398 to induce apoptosis is greater than that of indomethacin. Both indomethacin and NS‐398 reduced the cell proliferation in a concentration‐dependent manner. The IC 50 values of NS‐398 (54.8+3.6 and 77.2±4. 9μM ) were significantly lower than those of indomethacin (206.3±43.0 and 180.3±22.6/ μM ) at P<0.01 in Colo320 and THRC cell lines, respectively. These findings suggest that NS‐398, a selective inhibitor of COX‐2, is a possible candidate for a chemopreventive agent with a potent apoptosis‐inducing effect and low nlcerogenic activity.