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.