Cytotoxicity and apoptosis induction of sodium fluoride in human promyelocytic leukemia (HL-60) cells

The role of sodium fluoride (NaF) in cytotoxicity and induction of apoptosis was investigated by treating human promyelocytic leukemia (HL-60) cells with varying concentrations of NaF, from 0 to 250 ppm for different periods (0-72 h). At lower concentrations (0-50 ppm), no significant cytotoxicity was observed in response to NaF treatment. However, at higher concentrations (100-250 ppm), NaF reduced cell viability, and decreased DNA and protein biosynthesis capability in cultured HL-60 cells. The growth inhibitory and antiproliferative effects of NaF appear to be attributable to its induction of apoptotic cell death, as NaF induced morphological changes, internucleosomal DNA fragmentation, and increased the proportion of hypodiploid cells. NaF treatment also gradually decreased the expression of the anti-apoptotic protein Bcl-2, and increased activation of caspase-3 and cleavage of poly (ADP-ribose) polymerase. These results provides important information towards understanding the mechanism by which NaF mediates cytotoxicity and apoptosis. (C) 2002 Elsevier Science B.V. All rights reserved.