title: The novel selenium heteropoly compound (NH₄)₄H₄[Se₂Mo₂V₄O₂₄]·7H₂O induces apoptosis of K562 cells.
abstract: The purpose of this study was to investigate the antitumor effects and mechanism of the selenium heteropoly compound (NH₄)₄H₄[Se₂Mo₂V₄O₂₄]·7H₂O (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 micro-culture tetrazolium assay; the IC50 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 signifi-cantly caused the accumulation of Ca²⁺, Mg²⁺ 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 Ca²⁺, Mg²⁺ and ROS concentration, a reduction in the pH value and MMP, and the NF-κB/IκB signaling pathway.
authors: College of Life Sciences and Key Laboratory for Cell Differentiation Regulation, Henan Normal University, Xinxiang, Henan 453007, PR China. junyingyang@yahoo.com.cn
authors: Junying
authors: J
authors: Yang
authors: Xianguang
authors: X
authors: Yang
authors: Jinyu
authors: J
authors: Fan
authors: Qingqing
authors: Q
authors: Zhao
authors: Cunshuan
authors: C
authors: Xu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D051550:I-kappa B Kinase / Q000378:metabolism; D020014:K562 Cells; D008274:Magnesium / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D016328:NF-kappa B / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D018036:Selenium Compounds / Q000737:chemistry / Q000494:pharmacology*; D015398:Signal Transduction; D017968:Vanadium Compounds / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C569095:(NH4)4H4(Se2Mo2V4O24).7H2O; D000970:Antineoplastic Agents; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D018036:Selenium Compounds; D017968:Vanadium Compounds; D045304:Cytochromes c; D051550:I-kappa B Kinase; D008274:Magnesium; D002118:Calcium