Induction of apoptosis by selenite and selenodiglutathione in HL-60 cells:Correlation with cytotoxicity

Effects of selenite and selenodiglutathione, an initial metabolite of selen ite, on the induction of apoptosis and cytotoxicity were investigated in hu man promyelocytic leukemia HL-60 cells. Treatment of selenite or selenodigl utathione resulted in concentration-dependent cytotoxicity, measured by lac tate dehydrogenase leakage assay, and by tetrazolium salt reduction assay. Selenodiglutathione has been shown to exert more cytotoxic effect than sele nite in both assay systems. Time-course study of cellular selenium uptake s uggests that the higher cytotoxicity of selenodiglutathione be largely due to faster and greater selenium uptake rate. Treatment with selenite or sele nodiglutathione also induced apoptosis in a dose-dependent manner, as detec ted by enzyme-linked immunosorbent assay and by DNA fragmentation assay. Th e dose-response data of apoptosis induced by selenite or selenodiglutathion e were similar to those of cytotoxicity, implicating a relationship between the induction of apoptosis and cytotoxicity. Zn, which is a well-known inh ibitor of apoptosis, dose-dependently blocked not only the induction of apo ptosis, but also the membrane damage induced by selenium, corroborating thi s hypothesis. It was noted that the inhibition of apoptosis by Zn exerted l ittle protective effect on cytotoxicity at higher concentrations of seleniu m, compared with a perfect protective effect at low concentration of seleni um. These results suggest that cytotoxicity induced by selenium may be part ially correlated with apoptosis.