Inhibition of NF-kappa B with proteasome inhibitors enhances apoptosis in human lung adenocarcinoma cells in vitro

Background: Nuclear factor-kappaB (NF-kappaB) nuclear translocation has an important role in preventing apoptotic cell death in some cancers. However, little is known about the role of NF-kappaB in non-small cell carcinoma. M aterials and Methods: Human lung adenocarcinoma cells were stimulated with tumor necrosis factor (TNF) alone or TNF with proteasome inhibitors to bloc k NF-kappaB translocation. Cytotoxicity assays, histone-associated DNA-frag mentation ELISA, immunoblots of poly-(ADP ribose)-polymerase (PARP) and ele ctron microscopy were used to evaluate apoptosis. Results: TNF induced I ka ppaB proteolysis and NF-kappaB nuclear translocation; however, this was blo cked by pretreatment with proteasome inhibitors. TNF alone was not cytotoxi c, bur when NF-kappaB was blocked TNF induced cell death. Specifically, the cytotoxicity was due to apoptosis as noted by increased DNA-fragmentation, degradation of PARP and characteristic morphology. Conclusions: Proteasome inhibition was an effective method to inhibit NF-kappaB activation in lung adenocarcinoma cells. TNF in conjunction with NF-kappaB inhibition was a p otent stimulus for apoptosis.