Sodium selenite induces apoptosis of human PC3 prostate cancer cells through activation of mixed lineage kinase 3

Although selenium compounds are well known to exert the anticancer effect through induction of apoptosis in prostate cancer cell, little is known about the signaling mechanism for this activity. We here showed that sodium selenite activates mixed lineage kinase-3 (MLK-3) in PC3 human prostate cancer cells. The PC3 cells stably transfected with dominant-negative form of MLK3 showed a less degree of activation of caspase, collapse of mitochondrial membrane potential, and release of cytochrome c triggered by sodium selenite, suggesting a crucial role of MLK3 in sodium selenite signaling to apoptotic cell death. Our findings identify a MLK3 as a novel pathway mediating selenium signaling to apoptosis in human prostate cancer cells.