Cisplatin inhibits the expression of X-chromosome-linked inhibitor of apoptosis protein in an oral carcinoma cell line.
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.
Matsumiya
T
T
Department of Dentistry and Oral Surgery, School of Medicine, Hirosaki University, Hirosaki, 036-8562, Japan.
Imaizumi
T
T
Yoshida
H
H
Kimura
H
H
Satoh
K
K
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis; D015152:Blotting, Northern / Q000379:methods; D015153:Blotting, Western / Q000379:methods; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism*; D061945:Caspase Inhibitors; D002945:Cisplatin / Q000627:therapeutic use*; D053938:DNA Fragmentation; D004791:Enzyme Inhibitors / Q000032:analysis; D015870:Gene Expression; D006801:Humans; D009062:Mouth Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D011506:Proteins / Q000032:analysis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured / Q000187:drug effects; D051636:X-Linked Inhibitor of Apoptosis Protein
D000970:Antineoplastic Agents; D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D011506:Proteins; D012333:RNA, Messenger; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; D002945:Cisplatin