Induction of apoptosis by sodium selenite in human acute promyelocytic leukemia NB4 cells: involvement of oxidative stress and mitochondria.
The mechanisms involved in the anti-carcinogenic activity of selenium remained to be elucidated. In the present study, we examined sodium selenite induced apoptosis and oxidative stress in human acute promyelocytic leukemia cell lines (NB4). Cell growth and viability were assessed by trypan blue exclusion and cell counting; apoptosis by DNA electrophoresis and analysis of intracellular DNA contents; reactive oxygen species and reduced glutathione in the cell were measured by lucigenin dependent chemoluminescent (CL) test and spectrophotometer; mitochondrial transmembrane potential was measured by flow cytometry. Sodium selenite could inhibit the growth and induce apoptosis of NB4 cells. Sodium selenite could increase the production of reactive oxygen species (ROS) in NB4 cells and decrease the level of intracellular reduced glutathione, but caused no change in the activity of antioxidant enzymes, superoxide dismutase (SOD), glutathione peroxidase (GPx). Sodium selenite enhanced the collapse of mitochondrial transmembrane potential (MTP), in parallel with the production of ROS. Finally antioxidant N-acetylcysteine (NAC) could inhibit the ROS production, MTP collapse and apoptosis in NB4 cells. Our results suggested that sodium selenite could induce apoptosis of NB4 cells through mitochondrial change mediated by production of reactive oxygen species within the cells.
Li
Jian
J
Hematology department, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Peking, China. leej93@yahoo.com.cn
Zuo
Lu
L
Shen
Ti
T
Xu
Cai-min
CM
Zhang
Zhi-nan
ZN
D000111:Acetylcysteine / Q000494:pharmacology; D000166:Acridines / Q000494:pharmacology; D017209:Apoptosis; D002455:Cell Division; D002470:Cell Survival; D053938:DNA Fragmentation; D004587:Electrophoresis, Agar Gel; D005434:Flow Cytometry; D016193:G1 Phase; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000473:pathology*; D008163:Luminescent Measurements; D008564:Membrane Potentials; D008928:Mitochondria / Q000502:physiology*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species; D018038:Sodium Selenite / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000166:Acridines; D017382:Reactive Oxygen Species; C033472:10,10'-dimethyl-9,9'-biacridinium; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005978:Glutathione; D018038:Sodium Selenite; D000111:Acetylcysteine