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 th e chemopreventive action of nonsteroidal antiinflammatory drugs (NSAID s), which exhibit cancer-preventive and tumor-regressive effects in th e human colon, The effect of NS-398, (2-cyclohexyloxy-4-nitrophenyl)me thanesulfonamide, which is a selective inhibitor of cyclooxygenase-2 ( COX-2), on the induction of apoptosis in two human colorectal cancer c ell lines (Colo320 and THRC) was determined. The apoptotic ratios (-fo ld vs, control value) of Colo320 in the presence of 100 mu M indometha cin and NS-398 were 3.3 +/- 1.5 and 9.0 +/- 0.94, and those of THRC we re 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 indomet hacin and NS-398 reduced the cell proliferation in a concentration-dep endent manner. The IC50 values of NS-398 (54.8 +/- 3.6 and 77.2 +/- 4. 9 mu M) were significantly lower than those of indomethacin (206.3 +/- 43.0 and 180.3 +/- 22.6 mu M) at P < 0.01 in Colo320 and THRC cell li nes, respectively. These findings suggest that NS-398, a selective inh ibitor of COX-2, is a possible candidate for a chemopreventive agent w ith a potent apoptosis-inducing effect and low ulcerogenic activity.