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Tumor-specific cytotoxicity and type of cell death induced by peplomycin in oral squamous cell carcinoma cell lines.

Abstract
The antitumor antibiotic peplomycin showed higher cytostatic antiproliferative effect on five cultured human oral squamous cell carcinoma (OSCC) cell lines (HSC-2, HSC-3, HSC-4, Ca9-22 and NA), as compared with three human oral normal cells (gingival fibroblast HGF, pulp cell HPC and periodontal ligament fibroblast HPLF). Although the antiproliferative activity of peplomycin declined with increasing cell density, peplomycin showed tumor-specific cytotoxicity at any cell density. The five OSCC cell lines showed considerable differences in sensitivity against peplomycin; the HSC-2 cells were the most sensitive, followed by the NA, HSC-3, Ca9-22 and HSC-4 cells. Peplomycin did not induce internucleosomal DNA fragmentation in any of the five OSCC cell lines, and only slightly modified caspase-3, -8 and -9 activities in the HSC-2, Ca9-22 and NA cell lines. Electron microscopy revealed that peplomycin induced the vacuolation of mitochondria accompanying electron lucent matrices lacking cristae and the enlargement of the endoplasmic reticulum in the HSC-2 cells. These data suggest that the anti-proliferative effect of peplomycin is time-dependent, and therefore prolonged treatment with peplomycin in combination with cytotoxic chemotherapeutic agents may induce greater cytotoxic action.
AuthorsYu Liu, Hiroshi Sakagami, Osamu Amano, Hirotaka Kikuchi, Yukio Nakamura, Mariko Ishihara, Yumiko Kanda, Shiro Kunii, Wei Zhang, Guangyan Yu
JournalAnticancer research (Anticancer Res) 2008 Jul-Aug Vol. 28 Issue 4B Pg. 2197-204 ISSN: 0250-7005 [Print] Greece
PMID18751395 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antibiotics, Antineoplastic
  • Peplomycin
Topics
  • Antibiotics, Antineoplastic (pharmacology)
  • Carcinoma, Squamous Cell (drug therapy, pathology, ultrastructure)
  • Cell Death (drug effects)
  • Cell Line, Tumor
  • Fibroblasts (cytology, drug effects)
  • Humans
  • Microscopy, Electron
  • Mouth Neoplasms (drug therapy, pathology, ultrastructure)
  • Peplomycin (pharmacology)

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