Abstract
Cisplatin is known to activate caspase-3 through the mitogen-activated kinase (MAPK) pathway. We found that X-chromosome-linked inhibitor of apoptosis protein (XIAP), a direct inhibitor of caspase-3, 7, and 9, is constitutively expressed in a cell line of oral squamous cell carcinoma, KOSC-2. Cisplatin treatment of the cells inhibited the expression of XIAP, and this was associated with DNA fragmentation. Overexpression of XIAP, by a transfection experiment, inhibited the cisplatin-induced apoptosis. We conclude that cisplatin induces apoptosis mediated not only by the activation of MAPK pathway but by the inhibition of XIAP.
MeSH terms
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Antineoplastic Agents / therapeutic use*
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Apoptosis
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Blotting, Northern / methods
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Blotting, Western / methods
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Carcinoma, Squamous Cell / drug therapy
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Carcinoma, Squamous Cell / metabolism*
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Caspase Inhibitors*
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Cisplatin / therapeutic use*
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DNA Fragmentation
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Enzyme Inhibitors / analysis
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Gene Expression
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Humans
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Mouth Neoplasms / drug therapy
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Mouth Neoplasms / metabolism*
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Proteins / analysis*
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Proteins / genetics
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RNA, Messenger / analysis
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Reverse Transcriptase Polymerase Chain Reaction
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Tumor Cells, Cultured / drug effects
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X-Linked Inhibitor of Apoptosis Protein
Substances
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Antineoplastic Agents
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Caspase Inhibitors
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Enzyme Inhibitors
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Proteins
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RNA, Messenger
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X-Linked Inhibitor of Apoptosis Protein
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XIAP protein, human
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Cisplatin