NF-kappaB activation is required for cisplatin-induced apoptosis in head and neck squamous carcinoma cells

FEBS Lett. 2006 Jan 9;580(1):311-8. doi: 10.1016/j.febslet.2005.12.012. Epub 2005 Dec 12.


This study demonstrates a requirement for NF-kappaB activation in cis-diamminedichloroplatinum (cisplatin)-induced apoptosis in human head and neck squamous cell carcinoma (HNSCC) cell lines. This conclusion was supported by the following observations: cisplatin induced IkappaBalpha degradation and NF-kappaB-dependent transcriptional activation prior to cell death; pyrrolidine dithiocarbamate (PDTC), a chemical inhibitor of NF-kappaB activation, prevented apoptosis; lactacystin, an inhibitor of IkappaBalpha degradation, also prevented apoptosis; and finally, the expression of a super-repressor mutant IkappaBalpha blocked apoptosis. The expression of tumor necrosis factor alpha (TNFalpha) was promoted by cisplatin treatment and was suppressed by PDTC treatment. In addition, a neutralizing antibody against TNFalpha protected cells from cisplatin-induced apoptosis. These findings suggest that NF-kappaB activation is required for cisplatin-induced apoptosis and TNFalpha may play an important role in NF-kappaB-mediated apoptosis in cisplatin-treated HNSCC cell lines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / analogs & derivatives
  • Acetylcysteine / pharmacology
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacology
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Autocrine Communication / drug effects
  • Carcinoma, Squamous Cell / metabolism*
  • Cell Line, Tumor
  • Cisplatin / pharmacology*
  • Cysteine Proteinase Inhibitors / pharmacology
  • Head and Neck Neoplasms / metabolism*
  • Humans
  • I-kappa B Proteins / antagonists & inhibitors
  • I-kappa B Proteins / metabolism
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism*
  • Signal Transduction / drug effects
  • Thiocarbamates / pharmacology
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / immunology


  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • Cysteine Proteinase Inhibitors
  • I-kappa B Proteins
  • NF-kappa B
  • NFKBIA protein, human
  • Thiocarbamates
  • Tumor Necrosis Factor-alpha
  • lactacystin
  • NF-KappaB Inhibitor alpha
  • Cisplatin
  • Acetylcysteine