title: NF-kappaB activation is required for cisplatin-induced apoptosis in head and neck squamous carcinoma cells.
abstract: 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.
authors.affiliation: Department of Biological Sciences, University of Ulsan, Nam-Gu, Ulsan 680-749, Republic of Korea.
authors.forename: Seong Bum
authors.initials: SB
authors.lastname: Kim
authors.forename: Jong Soo
authors.initials: JS
authors.lastname: Kim
authors.forename: Ji Hye
authors.initials: JH
authors.lastname: Lee
authors.forename: Won Joon
authors.initials: WJ
authors.lastname: Yoon
authors.forename: Dong Seuk
authors.initials: DS
authors.lastname: Lee
authors.forename: Myoung Seok
authors.initials: MS
authors.lastname: Ko
authors.forename: Byung Suk
authors.initials: BS
authors.lastname: Kwon
authors.forename: Dae Hwa
authors.initials: DH
authors.lastname: Choi
authors.forename: Hong Rae
authors.initials: HR
authors.lastname: Cho
authors.forename: Byung Ju
authors.initials: BJ
authors.lastname: Lee
authors.forename: Dae Kyun
authors.initials: DK
authors.lastname: Chung
authors.forename: Hyeon Woo
authors.initials: HW
authors.lastname: Lee
authors.forename: Jeong Woo
authors.initials: JW
authors.lastname: Park
mesh_terms: 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
chemical_list: 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