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  • Title: Inhibition of NF-kappa B with proteasome inhibitors enhances apoptosis in human lung adenocarcinoma cells in vitro.
    Author: Milligan SA, Nopajaroonsri C.
    Journal: Anticancer Res; 2001; 21(1A):39-44. PubMed ID: 11299767.
    Abstract:
    BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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