Effects of
selenite and
selenodiglutathione, an initial metabolite of
selenite, on the induction of apoptosis and cytotoxicity were investigated in human promyelocytic
leukemia HL-60 cells. Treatment of
selenite or
selenodiglutathione resulted in concentration-dependent cytotoxicity, measured by
lactate dehydrogenase leakage assay, and by
tetrazolium salt reduction assay.
Selenodiglutathione has been shown to exert more cytotoxic effect than
selenite in both assay systems. Time-course study of cellular
selenium uptake suggests that the higher cytotoxicity of
selenodiglutathione be largely due to faster and greater
selenium uptake rate. Treatment with
selenite or
selenodiglutathione also induced apoptosis in a dose-dependent manner, as detected by
enzyme-linked
immunosorbent assay and by DNA fragmentation assay. The dose-response data of apoptosis induced by
selenite or
selenodiglutathione were similar to those of cytotoxicity, implicating a relationship between the induction of apoptosis and cytotoxicity. Zn, which is a well-known inhibitor of apoptosis, dose-dependently blocked not only the induction of apoptosis, but also the membrane damage induced by
selenium, corroborating this hypothesis. It was noted that the inhibition of apoptosis by Zn exerted little protective effect on cytotoxicity at higher concentrations of
selenium, compared with a perfect protective effect at low concentration of
selenium. These results suggest that cytotoxicity induced by
selenium may be partially correlated with apoptosis.