Involvement of cellular apoptotic machineries mediated by selenocompounds in HL-60 cells

Abstract

Recent evidences suggest that chemopreventive activities of selenocompounds might associate with apoptotic processes. Our previous studies have found that selenocompounds are potent inducers of apoptosis and exert a cytotoxic effect. Present investigations elucidated the response of cellular apoptotic machineries which was induced by organoselenuim, methylselenocysteine (MSC) or inorganic selenite in human promyelogenic leukemia (HL-60) cells. The treatment of MSC resulted in increase of DNA double strand break and activation of poly(ADP-ribose) polymerase (PARP). In addition, it caused processing and activation of caspase-3, apoptotic cleavage of PARP, and increase of apoptotic morphology. These apoptotic features were efficiently inhibited by the specific protease inhibitors including caspase inhibitor, z-VAD-fmk, and serine protease inhibitor, AAPV-cmk. In contrast, selenite didn``t involve proteolytic machineries, however it specifically degraded the PARP. These results suggest that caspase-3 and serine protease play an important role in MSC mediated apoptosis. Moreover, there are some processes other than apoptosis by which selenite exerts cell death and those probably include necrotic cell death.