Abstract
The aim of this study was to understand the molecular requirements for cisplatin-induced apoptosis in human head and neck squamous cell carcinoma (HNSCC) cell death. Cisplatin induced apoptosis in HNSCC cell lines, HSC-2, HSC-3 and HSC-4 in a dose-dependent manner. However, cisplatin did not induce the expression of Fas-ligand mRNA or upregulation of Fas protein. By caspase activation assays, cisplatin induced Caspase-3 (Casp-3), -8 and -9 activation. In all three lines tested, the use of a specific inhibitor of Casp-9 almost completely blocked cisplatin-induced apoptosis, while the use of Casp-3 and -8 inhibitors resulted in a partial blockade of cisplatin-induced apoptosis. Our results strongly suggest that Casp-9-dependent apoptosis plays an important role in cisplatin-induced HNSCC apoptosis.
MeSH terms
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Apoptosis / drug effects*
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Carcinoma, Squamous Cell / enzymology
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Carcinoma, Squamous Cell / genetics
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Carcinoma, Squamous Cell / metabolism
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Carcinoma, Squamous Cell / pathology*
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Caspase 3
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Caspase 8
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Caspase 9
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Caspase Inhibitors
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Caspases / metabolism*
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Cisplatin / pharmacology*
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Dose-Response Relationship, Drug
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Enzyme Activation / drug effects
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Fas Ligand Protein
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Gene Expression Regulation, Neoplastic / drug effects
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Head and Neck Neoplasms / enzymology
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Head and Neck Neoplasms / genetics
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Head and Neck Neoplasms / metabolism
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Head and Neck Neoplasms / pathology*
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Humans
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Membrane Glycoproteins / genetics
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Time Factors
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Tumor Cells, Cultured
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fas Receptor / metabolism
Substances
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Caspase Inhibitors
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FASLG protein, human
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Fas Ligand Protein
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Membrane Glycoproteins
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RNA, Messenger
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fas Receptor
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CASP3 protein, human
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CASP8 protein, human
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CASP9 protein, human
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Caspase 3
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Caspase 8
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Caspase 9
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Caspases
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Cisplatin