Sodium salicylate inhibits NF-kappaB and induces apoptosis in PC12 cells.
Sodium salicylate (NaSal) is an effective analgetic and antiinflammatory drug. Beside its well-known inhibitory effect on the cyclooxigenase enzymes, it influences the activity of other signal transduction proteins including nuclear factor kappa B (NF-kappaB) transcription factor. NF-kappaB is found in the cytoplasm bound to an inhibitory protein, inhibitory kappa B (IkappaB). After its phosphorylation, IkappaB is degraded and the released NF-kappaB translocates into the nucleus. Sodium salicylate inhibits the degradation of IkappaB, thus, NF-kappaB activation cannot occur. According to previous observations, the inhibition of this activation can lead to apoptosis. The main goals of this study were to demonstrate that inhibition of NF-kappaB by sodium salicylate decreases the viability of rat phaeochromocytoma PC12 cells and to investigate the nature of cell damage and death. PC12 cells were treated with different concentrations of sodium salicylate (1-20 mM). Higher concentrations (10-20 mM) killed PC12 cells in a dose-dependent manner. The assessments were done by direct cell counting in a Burker chamber and by the WST-1 cytotoxicity assay. We also found a decreased NF-kappaB activity after sodium salicylate treatment by electrophoretic mobility shift assay (EMSA). The cells treated with sodium salicylate were undergoing apoptosis as seen on our records obtained by time-lapse videomicroscopy as well as shown by DNA fragmentation experiments. The decreased DNA binding activity of NF-kappaB indicates that the inhibition of NF-kappaB can play a role in these processes.
Kiss
K
K
Department of Medical Biology, Faculty of Medicine, University of Pécs, Szigeti u. 12., H-7624 Pécs, Hungary.
Kiss
J
J
Rudolf
E
E
Cervinka
M
M
Szeberényi
J
J
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D016716:PC12 Cells; D051381:Rats; D012980:Sodium Salicylate / Q000008:administration & dosage*
D016328:NF-kappa B; D012980:Sodium Salicylate