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)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 IC₅₀ 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.