Cytotoxic Activity of Selected Trifluoromethyl Ketones Against Oral Tumor Cells

• Published in: Anticancer research 2006-11, Vol.26 (6B), p.4335-4341
• Main Authors: IDEO, Atsushi, SASAKI, Masahiro, NAKAMURA, Chika, MORI, Kazumasa, SHIMADA, Jun, KANDA, Yumiko, KUNII, Shiro, KAWASE, Masami, SAKAGAMI, Hiroshi
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Carcinoma, Squamous Cell - pathology; Drug Screening Assays, Antitumor; Electrophoresis, Agar Gel; HL-60 Cells; Humans; Ketones - pharmacology; Medical sciences; Microscopy, Electron; Mouth Neoplasms - pathology; Tumors
• ISSN: 0250-7005; 1791-7530

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 α-diketone ( TF1 , CF 3 COCOPh) and α-hydroxy ketones ( TF2 , CF 3 CH(OH)COPh; TF3 , CF 3 CH(OH)COCH 2 Ph) showed higher tumor-specific cytotoxic activity than the corresponding non-fluorinated analogs ( TF5 , CH 3 COCOPh; TF6 , CH 3 CH(OH)COPh), while the anti-tumor potency of trifluoromethyl ketone ( TF4 , CF 3 COCH 2 Ph,) 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 internucleosomal DNA fragmentation nor activated caspase-3. The cytotoxic activities of TF1-3 were not significantly affected by FeCl 3 . 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 .