The anti-apoptotic property of NS-398 at high dose can be mediated in part through NF-κB activation, hsp70 induction and a decrease in caspase-3 activity in human osteosarcoma cells
Affiliations: Laboratoire de Biochimie, UPRES EA 1085, Faculte de Pharmacie, 87025 Limoges Cedex, France
- Published online on: June 1, 2002 https://doi.org/10.3892/ijo.20.6.1255
- Pages: 1255-1262
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Non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to produce an anti-proliferative and pro-apoptotic effect on different types of cancer cell lines. Previously, we demonstrated that high dose of NS-398 (100 μM), a selective cyclooxygenase-2 inhibitor, induced a cell cycle slowing or arrest and, in contrast to low dose (10 μM), a marked decrease in apoptosis in human 1547 osteosarcoma cells. In this study, we investigated particularly the effect of 100 μM NS-398 on p53 and p21 expression, caspase activities and nuclear factor-κB (NF-κB). We found a correlation between p53, p21 mRNA expression and NF-κB activation and, we observed an induction of heat shock protein 70 expression with a large decrease in caspase-3 activity after 100 μM NS-398 treatment. Moreover, the inhibition of apoptosis was correlated with an increase in bcl-2/bax ratio. Our new findings confirm the novel anti-apoptotic property of NS-398 at 100 μM, as we previously found, which contrasts to the described NS-398 pro-apoptotic effect on other cancer cell lines.