Introduction.Tumor necrosis factor (TNF-α)-induced apoptosis is limited by its coactivation of nuclear factor kappa B (NF-κB)-dependent anti-apoptotic genes. Sodium salicylate (NaSal) inhibits NF-κB activation by limiting phosphorylation and degradation of its bound inhibitor protein, IκB-α. We examined whether NaSal enhances TNF-α-induced apoptosis in cultured human pancreatic cancer cell lines.Methods.Two cultured human pancreatic cancer cell lines were studied. PANC-1 and BxPC-3 cells were serum-starved for 12 h, pretreated or not for 1 h with NaSal (5–20 mM), and then stimulated with recombinant human TNF-α (400 units/ml). Western blots of cytoplasmic lysates were performed to demonstrate IκB-α phosphorylation and degradation. Western blots of nuclear extracts were performed to assess nuclear translocation of NF-κB. In separate cultures, apoptosis was measured 4.5 h after TNF-α stimulation by both ELISA detection of interhistone DNA fragments and flow cytometry with propidium iodide staining.Results.TNF-α induced IκB-α phosphorylation and degradation, which was inhibited by NaSal in both cell lines. TNF-α-induced apoptosis (DNA fragmentation) increased significantly when BxPC-3 cells were pretreated with NaSal. Flow cytometry confirmed this, demonstrating increases in apoptotic cell fractions: 8.5% (untreated), 9.3% (TNF-α alone), 14.9% (15 mM NaSal), and 22.9% (NaSal and TNF-α). In contrast, no increases in apoptosis were measured in the PANC-1 cell line among the various treatment groups.Conclusions.NaSal enhances TNF-α-induced apoptosis while inhibiting IκB-α phosphorylation and degradation in BxPC-3 human pancreatic cancer cells.