Inhibition of NF-kappa B with proteasome inhibitors enhances apoptosis in human lung adenocarcinoma cells in vitro
Milligan, S.A.; Nopajaroonsri, C.
Anticancer Research 21(1a): 39-44
2001
ISSN/ISBN: 0250-7005 PMID: 11299767 Document Number: 530225
Nuclear factor-kappa B (NF-kappa B) nuclear translocation has an important role in preventing apoptotic cell death in some cancers. However, little is known about the role of NF-kB in non-small cell carcinoma. Human lung adenocarcinoma cells were stimulated with tumor necrosis factor (TNF) alone or TNF with proteasome inhibitors to block NF-kappa B translocation. Cytotoxicity assays, histone-associated DNA-fragmentation ELISA, immunoblots of poly-(ADP ribose)-polymerase (PARP) and electron microscopy were used to evaluate apoptosis. TNF induced I kappa B proteolysis and NF-kappa B nuclear translocation; however, this was blocked by pretreatment with proteasome inhibitors. TNF alone was not cytotoxic, but when NF-kappa B 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. Proteasome inhibition was an effective method to inhibit NF-kappa B activation in lung adenocarcinoma cells. TNF in conjunction with. NF-kappa B inhibition was a potent stimulus for apoptosis.