The antitumor effects of selenium compound Na5SeV5O18.3H20 in K562 cell.
With an approach to study the anti-tumor effects and mechanism of selenium compound, we investigated the anti-tumor activity and mechanism of Na5SeV5O18.H20 (NaSeVO) in K562 cells. The results showed that 0.625-20 mg/L NaSeVO could significantly inhibit the proliferation of K562 cells in vitro in a time- and concentration-dependent manner as determined by microculture tetrazolium (MTT) assay, the IC50 values were 14.41 (4.45-46.60) and 3.45 (2.29-5.22) mg/L after 48 h and 72 h treatment with NaSeVO respectively. In vivo experiments demonstrated that i.p. administration of 5, 10 mg/kg NaSeVO exhibited an significant inhibitory effect on the growth of transplantation tumor sarcoma 180 (S180) and hepatoma 22 (H22) in mice, with inhibition rate 26.8% and 58.4% on S180 and 31.3% and 47.4% on H22, respectively. Cell cycle studies indicated that the proportion of G0/G1 phase was increased at 2.5 mg/ L while decreased at 10 mg/L after treatment for 24, 48 h. Whereas S phase was decreased at 2.5-5 mg/L and markedly increased at 10 mg/L after treatment for 48 h. After treatment for 24 h, 10 mg/L NaSeVO also markedly increased S and G2/M phases. Take together, the result clearly showed that NaSeVO markedly increased S and G2/M phases at 10 mg/L. The study of immunocytochemistry showed that the expression bcl-2 is significantly inhibited by 10 mg/L NaSeVO, and bax increased. Morphology observation also revealed typical apoptotic features. NaSeVO also significantly caused the accumulation of Ca2+ and Mg2+, reactive oxygen species (ROS) and the reduction of pH value and mitochondrial membrane potential in K562 cells as compared with control by confocal laser scanning microscope. These results suggest that NaSeVO has anti-tumor effects and its mechanism is attributed partially to apoptosis induced by the elevation of intracellular Ca2+, Mg2+ and ROS concentration, and a reduction of pH value and mitochondria membrane potential (MMP).
Yang
Jun-Ying
JY
School of Life Sciences, Lanzhou University, Lanzhou 730000, P R China.
Wang
Zi-Ren
ZR
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000648:ultrastructure; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D020128:Inhibitory Concentration 50; D007274:Injections, Intraperitoneal; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D020014:K562 Cells; D008274:Magnesium / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008854:Microscopy, Electron; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000502:physiology; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D018036:Selenium Compounds / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D014638:Vanadates / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D000970:Antineoplastic Agents; C517309:Na5SeV5O18; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D018036:Selenium Compounds; D051028:bcl-2-Associated X Protein; D014638:Vanadates; D008274:Magnesium; D002118:Calcium