Se-methylselenocysteine induces apoptosis mediated by reactive oxygen species in HL-60 cells

Recent studies have implicated apoptosis as one of the most plausible mecha nisms of the chemopreventive effects of selenium compounds, and reactive ox ygen species (ROS) as important mediators in apoptosis induced by various s timuli. In the present study, we demonstrate that Se-methylselenoeysteine ( MSC), one of the most effective selenium compounds at chemoprevention, indu ced apoptosis in HL-60 cells and that ROS plays a crucial role in MSC-induc ed apoptosis. The uptake of MSC by HL-60 cells occurred quite early, reachi ng the maximum within 1 h. The dose-dependent decrease in cell viability wa s observed by MSC treatment and was coincident with increased DNA fragmenta tion and sub-G(1) population. 50 muM of MSC was able to induce apoptosis in 48% of cell population at a 24 h time point. Moreover, the release of cyto chrome c from mitochondria and the activation of caspase-3 and caspase-9 we re also observed. The measurement of ROS by dichloro fluorescein fluorescen ce revealed that dose- and time-dependent increase in ROS was induced by MS C. N-acetylcysteine, glutathione, and deferoxamine blocked cell death, DNA fragmentation, and ROS generation induced by MSC. Moreover, N-acetyleystein e effectively blocked caspase-3 activation and the increase of the sub-G(1) population induced by MSC. These results imply that ROS is a critical medi ator of the MSC-induced apoptosis in HL-60 cells. (C) 2001 Elsevier Science Inc.