Comparative analysis of cell death induction by cisplatin and 5-FU in human oral squamous and hepatocellular carcinoma cell lines.

Abstract

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.

• Authors: Masahiko Okamura, Jun Shimada, Hiroshi Sakagami
• Journal: Anticancer research (Anticancer Res) 2008 Jan-Feb Vol. 28 Issue 1A Pg. 253-9 ISSN: 0250-7005 [Print] Greece
• PMID: 18383853 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antimetabolites, Antineoplastic
• Antineoplastic Agents
• Isoenzymes
• Caspases
• Cisplatin
• Fluorouracil

Topics

• Antimetabolites, Antineoplastic (pharmacology)
• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Carcinoma, Hepatocellular (drug therapy, pathology)
• Carcinoma, Squamous Cell (drug therapy, pathology)
• Caspases (metabolism)
• Cell Line, Tumor
• Cisplatin (pharmacology)
• DNA Fragmentation (drug effects)
• Enzyme Activation
• Fluorouracil (pharmacology)
• Humans
• Isoenzymes
• Liver Neoplasms (drug therapy, pathology)
• Mouth Neoplasms (drug therapy, pathology)