Comparative analysis of cell death induction by cisplatin and 5-FU in human oral squamous and hepatocellular carcinoma cell lines.
We established the optimal conditions for the induction of cell death by cisplatin (CDDP) and 5-fluorouracil (5-FU) in human oral squamous cell carcinoma (HSC-2, HSC-3, HSC-4) and human hepatocellular carcinoma (HepG2) cell lines. HSC-3 cells were the most sensitive to 48 hours' continuous treatment with CDDP, followed by HepG2, HSC-2 and HSC-4 cells. On the other hand, HSC-4 cells were the most sensitive to 48-hour continuous treatment with 5-FU, followed by HSC-2, HSC-3 and HepG2 cells. CDDP induced internucleosomal DNA fragmentation in HSC-2 and HSC-3 cells, but not in HSC-4 cells, while 5-FU failed to induce internucleosomal DNA fragmentation in all of these cells. The treatment of HSC-2, HSC-3 and HSC-4cells with CDDP for 12 hours (followed by incubation for 36 hours without CDDP) showed comparable magnitude of cytotoxicity and caspase-3 activation with that attained by continuous 48-hour CDDP treatment. On the other hand, the cytotoxicity of 5-FU depended both on the dose and the exposure time. The present study demonstrate that the most effective treatment time is 12 hours for CDDP and much longer for 5-FU in all studied cell lines, underlining the importance of optimizing the treatment time for each chemotherapeutic agent.
Okamura
Masahiko
M
Division of Oral Maxillofacial Surgery, Department of Diagnostic and Therapeutic Sciences, Meikai University School of Dentistry, Sakado, Saitama 350-0283, Japan.
Shimada
Jun
J
Sakagami
Hiroshi
H
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D053938:DNA Fragmentation / Q000187:drug effects; D004789:Enzyme Activation; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D007527:Isoenzymes; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000473:pathology
D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D007527:Isoenzymes; D020169:Caspases; D002945:Cisplatin; D005472:Fluorouracil