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Induction of cell death by combination treatment with cisplatin and 5-fluorouracil in a human oral squamous cell carcinoma cell line.

Abstract
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.
AuthorsMasahiko Okamura, Masaki Kobayashi, Fumika Suzuki, Jun Shimada, Hiroshi Sakagami
JournalAnticancer research (Anticancer Res) 2007 Sep-Oct Vol. 27 Issue 5A Pg. 3331-7 ISSN: 0250-7005 [Print] Greece
PMID17970078 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Biogenic Polyamines
  • Isoenzymes
  • Caspases
  • Cisplatin
  • Fluorouracil
Topics
  • Antineoplastic Combined Chemotherapy Protocols (administration & dosage)
  • Apoptosis (drug effects)
  • Biogenic Polyamines (metabolism)
  • Carcinoma, Squamous Cell (drug therapy, metabolism, pathology)
  • Caspases (metabolism)
  • Cell Line, Tumor
  • Cisplatin (administration & dosage)
  • DNA Fragmentation
  • Drug Administration Schedule
  • Enzyme Activation
  • Fluorouracil (administration & dosage)
  • HL-60 Cells
  • Humans
  • Isoenzymes (metabolism)
  • Mouth Neoplasms (drug therapy, metabolism, pathology)

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