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

This study demonstrates a requirement for NF-κB 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 IκBα degradation and NF-κB-dependent transcriptional activation prior to cell death; pyrrolidine dithiocarbamate (PDTC), a chemical inhibitor of NF-κB activation, prevented apoptosis; lactacystin, an inhibitor of IκBα degradation, also prevented apoptosis; and finally, the expression of a super-repressor mutant IκBα blocked apoptosis. The expression of tumor necrosis factor α (TNFα) was promoted by cisplatin treatment and was suppressed by PDTC treatment. In addition, a neutralizing antibody against TNFα protected cells from cisplatin-induced apoptosis. These findings suggest that NF-κB activation is required for cisplatin-induced apoptosis and TNFα may play an important role in NF-κB-mediated apoptosis in cisplatin-treated HNSCC cell lines.