Sodium salicylate inhibits NF-κB and induces apoptosis in PC12 cells

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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-κB) transcription factor. NF-κB is found in the cytoplasm bound to an inhibitory protein, inhibitory kappa B (IκB). After its phosphorylation, IκB is degraded and the released NF-κB translocates into the nucleus. Sodium salicylate inhibits the degradation of IκB, thus, NF-κB 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-κB 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 Bürker chamber and by the WST-1 cytotoxicity assay. We also found a decreased NF-κB 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-κB indicates that the inhibition of NF-κB can play a role in these processes.