Cytotoxic activity of selected trifluoromethyl ketones against oral tumor cells.
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.
Ideo
Atsushi
A
Division of Oral and Maxillofacial Surgery, Meikai University School of Dentistry, Sakado, Saitama 350-0283, Japan.
Sasaki
Masahiro
M
Nakamura
Chika
C
Mori
Kazumasa
K
Shimada
Jun
J
Kanda
Yumiko
Y
Kunii
Shiro
S
Kawase
Masami
M
Sakagami
Hiroshi
H
D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D004354:Drug Screening Assays, Antitumor; D004587:Electrophoresis, Agar Gel; D018922:HL-60 Cells; D006801:Humans; D007659:Ketones / Q000494:pharmacology*; D008854:Microscopy, Electron; D009062:Mouth Neoplasms / Q000473:pathology*
D007659:Ketones