Inorganic Selenium Induces Nonapoptotic Programmed Cell Death in PC-3 Prostate Cancer Cells Associated with Inhibition of Glycolysis

Previous studies have shown that selenite, a representative of inorganic form selenium, exerts its anticancer effect by inducing apoptosis in androgen-dependent LNCaP prostate cancer cells, but few studies have determined the nature of cell death induced by selenite in metastatic androgen-refractory PC-3 cells. Our study showed that necrosis-like cell death rather than apoptosis, pyroptosis, or autophagic cell death was caused by selenite in PC-3 cells. Mechanistically, this type of cell death was caused by ATP depletion (26.28 +/- 3.39 nmol/mg of control versus 9.12 +/- 2.44 nmol/mg of 10 mu M selenite treatment) that resulted from phosphofructokinase activity reduction (100.17 +/- 0.17% of control versus 21.74 +/- 6.65% of 10 mu M selenite treatment). Our study also showed that ROS production is necessary for the decrease in cellular ATP levels and in phosphofructokinase activity. To our knowledge, this is the first study showing that selenite can induce necrosis-like cell death in PC-3 cells. Our findings support selenite as an effective compound for the therapy of apoptosis-resistant prostate cancer.