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Cytotoxic activity of selected trifluoromethyl ketones against oral tumor cells.

Abstract
Several trifluoromethyl ketones (TF1-4) and related non-fluorinated ketones (TF5 and 6) were tested for their relative cytotoxicity on four human tumor cell lines (oral squamous cell carcinoma HSC-2, HSC-3, HSC-4 and promyelocytic leukemia HL-60) and three normal human cells [gingival fibroblasts (HGF), pulp cells (HPC) and periodontal ligament fibroblasts (HPLF)]. Trifluoromethylated a-diketone (TF1, CF3COCOPh) and alpha-hydroxy ketones (TF2, CF3CH(OH)COPh; TF3, CF3CH(OH)COCH2Ph) showed higher tumor-specific cytotoxic activity than the corresponding non-fluorinated analogs (TF5, CH3COCOPh; TF6, CH3CH(OH)COPh), while the anti-tumor potency of trifluoromethyl ketone (TF4, CF3COCH2Ph) was lower. Among four tumor cell lines, HL-60 cells were the most sensitive to TF1-4, followed by HSC-2 and HSC-3 cells. HSC-4 cells were the most resistant in most cases. Agarose gel electrophoresis showed that TF1-3 did not induce intemucleosomal DNA fragmentation nor activated caspase-3. The cytotoxic activities of TF1-3 were not significantly affected by FeCl3. Electron microscopy of TF2- or 3-treated HL-60 cells showed the development of autophagosomes in HL-60 cells, without the production of an apoptotic body, or affecting the mitochondria and cell surface microvilli. The autophagy inhibitor, 3-methyladenine (3-MA), partially inhibited the TF2- or 3-induced cytotoxicity. These data suggest the induction of non-apoptotic cell death by TF2 or 3.
AuthorsAtsushi Ideo, Masahiro Sasaki, Chika Nakamura, Kazumasa Mori, Jun Shimada, Yumiko Kanda, Shiro Kunii, Masami Kawase, Hiroshi Sakagami
JournalAnticancer research (Anticancer Res) 2006 Nov-Dec Vol. 26 Issue 6B Pg. 4335-41 ISSN: 0250-7005 [Print] Greece
PMID17201152 (Publication Type: Journal Article)
Chemical References
  • Ketones
Topics
  • Carcinoma, Squamous Cell (pathology)
  • Drug Screening Assays, Antitumor
  • Electrophoresis, Agar Gel
  • HL-60 Cells
  • Humans
  • Ketones (pharmacology)
  • Microscopy, Electron
  • Mouth Neoplasms (pathology)

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