Involvement of caspases in 5-FU induced apoptosis in an oral cancer cell line.
Although many anticancer drugs have been reported to induce apoptosis in cancer cells, the underlying mechanism remains unclear (1-3). Recent studies have revealed that the caspase family of cysteine proteases have been shown to play an important role in the regulation of several apoptotic processes. Thus, the present study investigated whether apoptosis induced by anticancer drugs is mediated by the activation of caspase cascade. NA cells, a squamous cell carcinoma cell line, were exposed to cisplatin (CDDP) or 5-fluorouracil (5-FU) with or without inhibitors of caspase 1, 3 and 8. Analysis of DNA fragmentation revealed that caspase inhibitors consistently inhibited DNA fragmentation induced by 5-FU. During the early stages of apoptosis, phosphatidylserine (PS) is translocated from the inner side of the plasma membrane to the cell surface. This PS externalization was markedly inhibited by treatment with caspase-8 inhibitor. These findings suggested that 5-FU induced apoptosis was mediated by the activation of a caspase cascade involving caspase 1, 3 and 8.
Ohtani
T
T
Second Department of Oral and Maxillofacial Surgery, School of Dentistry, Showa University, Tokyo, Japan.
Hatori
M
M
Ito
H
H
Takizawa
K
K
Kamijo
R
R
Nagumo
M
M
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D006690:Bisbenzimidazole; D002294:Carcinoma, Squamous Cell; D020170:Caspase 1 / Q000378:metabolism; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D002467:Cell Nucleus; D002945:Cisplatin / Q000494:pharmacology; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D053938:DNA Fragmentation / Q000187:drug effects; D005434:Flow Cytometry / Q000379:methods; D005456:Fluorescent Dyes; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D013194:Staining and Labeling / Q000379:methods; D014062:Tongue Neoplasms; D014407:Tumor Cells, Cultured
D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D005456:Fluorescent Dyes; C505407:CASP3 protein, human; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases; D020170:Caspase 1; D006690:Bisbenzimidazole; D002945:Cisplatin; D005472:Fluorouracil