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 μM
selenite treatment) that resulted from
phosphofructokinase activity reduction (100.17 ± 0.17% of control versus 21.74 ± 6.65% of 10 μM
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.