NF-kappaB activation is required for cisplatin-induced apoptosis in head and neck squamous carcinoma cells.
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.
Kim
Seong Bum
SB
Department of Biological Sciences, University of Ulsan, Nam-Gu, Ulsan 680-749, Republic of Korea.
Kim
Jong Soo
JS
Lee
Ji Hye
JH
Yoon
Won Joon
WJ
Lee
Dong Seuk
DS
Ko
Myoung Seok
MS
Kwon
Byung Suk
BS
Choi
Dae Hwa
DH
Cho
Hong Rae
HR
Lee
Byung Ju
BJ
Chung
Dae Kyun
DK
Lee
Hyeon Woo
HW
Park
Jeong Woo
JW
D000111:Acetylcysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D019898:Autocrine Communication / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D006258:Head and Neck Neoplasms / Q000378:metabolism*; D006801:Humans; D020672:I-kappa B Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013859:Thiocarbamates / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D015853:Cysteine Proteinase Inhibitors; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D013859:Thiocarbamates; D014409:Tumor Necrosis Factor-alpha; C067713:lactacystin; D000072000:NF-KappaB Inhibitor alpha; D002945:Cisplatin; D000111:Acetylcysteine