Dose-dependent modulation of apoptosis and cyclooxygenase-2 expression in human 1547 osteosarcoma cells by NS-398, a selective cyclooxygenase-2 inhibitor

A selective cyclooxygenase-2 (COX-2) inhibitor, NS-398, was shown to produc e an anti-proliferative and pro-apoptotic effect on different types of cell lines. We describe the presence of COX-I and COX-2 pathways in the human o steosarcoma 1547 cell line, as well as the conflicting effects of NS-398 (1 0, 50 and 100 muM) on programmed cell death, PGE? release and COX-2 express ion in 1547 cells cultured under apoptotic conditions. We demonstrate a lin k between the effects of 10 and 100 muM NS-398 on cell apoptosis, PGE, rele ase, and expression of COX-2 in 1547 cells undergoing apoptosis. At 10 muM, NS-398 acted as a selective COX-2 inhibitor moderately increasing apoptosi s without any effect on COX-2 expression. In contrast, at 100 muM, NS-398 i nduced a cell cycle slowing or arrest, strongly enhanced COX-2 expression w hich was associated with a high PGE, release and a marked decrease in apopt osis. This latter property of NS-398 at 100 muM in 1547 human osteosarcoma cells is novel compared to the described NS-398 pro-apoptotic effect on oth er cell lines.