Apoptosis induced by NS-398, a selective cyclooxygenase-2 inhibitor, in human colorectal cancer cell lines.
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)methanesulfonamide, 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 microM 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 IC50 values of NS-398 (54.8 +/- 3.6 and 77.2 +/- 4.9 microM) were significantly lower than those of indomethacin (206.3 +/- 43.0 and 180.3 +/- 22.6 microM) 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 ulcerogenic activity.
Hara
A
A
Department of Pathology, Gifu University School of Medicine.
Yoshimi
N
N
Niwa
M
M
Ino
N
N
Mori
H
H
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000473:pathology*; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000633:toxicity*; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007052:Ibuprofen / Q000633:toxicity; D007213:Indomethacin / Q000633:toxicity; D007527:Isoenzymes / Q000378:metabolism*; D008565:Membrane Proteins; D009578:Nitrobenzenes / Q000633:toxicity*; D010894:Piroxicam / Q000633:toxicity; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D013449:Sulfonamides / Q000633:toxicity*; D014407:Tumor Cells, Cultured
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D009578:Nitrobenzenes; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D010894:Piroxicam; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D007052:Ibuprofen; D007213:Indomethacin