Induction of cell death by combination treatment with cisplatin and 5-fluorouracil in a human oral squamous cell carcinoma cell line.
The possible apoptosis-inducing activity of several sequential treatments of cisplatin (CDDP) and 5-fluorouracil (5-FU) against the human oral squamous cell carcinoma HSC-2 cell line was investigated. The following three combination treatments (CT) were used: simultaneous treatment with CDDP and 5-FU (for 72 hours) (CT-1), CDDP treatment (24 hours) followed by 5-FU treatment (48 hours) (CT-2) and 5-FU treatment (24 hours) followed by CDDP treatment (48 hours) (CT-3). CT-1 produced the highest cytotoxicity, followed by CT-3 and CT-2. No treatment induced any detectable internucleosomal DNA fragmentation, and caspase-3,-8 and -9 were activated to a much lesser extent than that attained using actinomycin D. High-performance liquid chromatography analysis demonstrated that 5-FU, as well as CT-1 and CT-2, preferentially reduced the intracellular concentration of putrescine. These results suggest that simultaneous treatment with CDDP and 5-FU induces lower level of apoptotic cell death in HSC-2 cells.
Okamura
Masahiko
M
Division of Oral Maxillofacial Surgery, Meikai University School of Dentistry, Sakado, Saitama 350-0283, Japan.
Kobayashi
Masaki
M
Suzuki
Fumika
F
Shimada
Jun
J
Sakagami
Hiroshi
H
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects*; D015317:Biogenic Polyamines / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage; D053938:DNA Fragmentation; D004334:Drug Administration Schedule; D004789:Enzyme Activation; D005472:Fluorouracil / Q000008:administration & dosage; D018922:HL-60 Cells; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
D015317:Biogenic Polyamines; D007527:Isoenzymes; D020169:Caspases; D002945:Cisplatin; D005472:Fluorouracil