The novel selenium heteropoly compound (NH 4) 4H 4[Se 2Mo 2V 4O 24] •7H 2O induces apoptosis of K562 cells

Abstract

The purpose of this study was to investigate the antitumor effects and mechanism of the selenium heteropoly compound (NH 4) 4H 4[Se 2Mo 2V 4O 24] •7H 2O (SeMoV) in K562 cells. The results showed that 0.313-10 mg/l SeMoV significantly inhibited the proliferation of K562 cells in vitro in a time- and concentration-dependent manner as determined by a microculture tetrazolium assay; the IC 50 values were 7.69 and 4.06 mg/l following 48 and 72 h of treatment with SeMoV, respectively. Analysis of the cell cycle indicated that the proportion of cells in the G0/G1 phase was decreased at 48 h whereas the proportion of cells in the S phase was increased following treatment for 24 and 48 h. A significant sub-G1 peak was observed at 5 mg/l for 24 h. Morphological observation revealed typical apoptotic features. SeMoV significantly caused the accumulation of Ca 2+, Mg 2+ and ROS, and a reduction in the pH value and the mitochondrial membrane potential (MMP) in the K562 cells compared with the control (p<0.01), as shown by confocal laser scanning microscopy. Experiments also showed that the expression of Bcl-2 was significantly inhibited by 20 mg/l SeMoV, while Bax expression increased. Meanwhile, the amount of cytochrome C and IκB in K562 cells was increased, while NF-κB expression was significantly decreased, following treatment with SeMoV for 24 h. The experiment implied that SeMoV had antitumor activity and its mechanism was attributed partially to apoptosis, which was induced by the elevation of the intracellular Ca 2+, Mg 2+ and ROS concentration, a reduction in the pH value and MMP, and the NF-κB/IκB signaling pathway.