NF-kappaB activation is related to the resistance of lung cancer cells to TNF-alpha-induced apoptosis

Biochem Biophys Res Commun. 2000 Jun 24;273(1):140-6. doi: 10.1006/bbrc.2000.2909.

Abstract

In diverse cell types, NF-kappaB transcription factors have been shown to have a role in regulating the apoptotic program, either as essential for the induction of apoptosis or, perhaps more commonly, as blockers of apoptosis. We investigated the role of NF-kappaB activation in the TNF-alpha-mediated apoptosis in lung cancer cells. TNF-alpha-resistant NCI-H157 cells became sensitized to TNF-alpha by prior treatment with cycloheximide, suggesting the presence of newly synthesized antiapoptotic protein(s). We next evaluated whether the transcription of antiapoptotic protein(s) depends on the activation of NF-kappaB. NF-kappaB activation was blocked by either adenovirus-mediated overexpression of IkappaBalpha superrepressor or pretreatment with proteasome inhibitor, MG132. Both methods of blocking NF-kappaB activation enhanced TNF-alpha-induced apoptosis in NCI-H157 cells. These results suggest that NF-kappaB activation confers resistance to TNF-alpha-mediated apoptosis in lung cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Apoptosis / drug effects*
  • Cycloheximide / pharmacology
  • Cysteine Endopeptidases / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Drug Resistance, Neoplasm
  • Enzyme Inhibitors / pharmacology
  • Humans
  • I-kappa B Proteins*
  • Lung Neoplasms / enzymology
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology*
  • Multienzyme Complexes / metabolism
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism*
  • Neoplasm Proteins / biosynthesis
  • Proteasome Endopeptidase Complex
  • Protein Processing, Post-Translational / drug effects
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / agonists
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Tumor Necrosis Factor-alpha / pharmacology*

Substances

  • DNA-Binding Proteins
  • Enzyme Inhibitors
  • I-kappa B Proteins
  • Multienzyme Complexes
  • NF-kappa B
  • NFKBIA protein, human
  • Neoplasm Proteins
  • Tumor Necrosis Factor-alpha
  • NF-KappaB Inhibitor alpha
  • Cycloheximide
  • Cysteine Endopeptidases
  • Proteasome Endopeptidase Complex