[Sodium selenite-induced oxidative stress and apoptosis in human acute promyelocytic leukemia NB4 cells].
OBJECTIVE
To explore sodium selenite-induced oxidative stress and apoptosis in human promyelocytic leukemia NB4 cells.


METHODS
The growth inhibition of NB4 cells was measured by MTT test. Apoptosis was determined morphologically by Giemsa stain and by DNA ladder formation in electrophoresis. Quantitation of apoptosis was determined by percentage of PI stained cells containing subdiploid amount of DNA measured by flow cytometry. Generation of reactive oxidative species (ROS) in NB4 cells was determined by lucigenin dependent chemoluminescent (CL) test. Spectrophotometer was used to measure the level of reduced glutathione, superoxide dismutase (SOD) and glutathione peroxidase in the cell.


RESULTS
Sodium selenite was shown to inhibit the growth of NB4 cells. Sodium selenite induced apoptosis with dose and time dependency: the ratio of subdiploid cells in control group was 1.3% +/- 0.7%. The 5 mumol.L-1 group was 10.4% +/- 1.4%, 10 mumol.L-1 group was 16% +/- 1%, and the 20 mumol.L-1 group was 27.3% +/- 0.8%. Sodium selenite (> or = 5 mumol.L-1) enhanced the ROS level markedly in NB4 cells (in 20 mumol.L-1 group ROS level was increased by 17 times, compared with control group), accompanied with decrease of reduced intracellular glutathione. These effects were time and dose dependent. N-acytlcysteine as an antioxidant was found to inhibit sodium selenite-induced oxidative stress and apoptosis in NB4 cells.


CONCLUSIONS
Sodium selenite can induce apoptosis of NB4 cells and would possibly be used as an agent for the treatment of malignancy. The main mechanism of action might be related to oxidative stress induced by sodium selenite, thereby, leading to apoptosis as shown in NB4 cells.
Li
Jian
J
Hematology Department, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100730, China.
Zuo
Lu
L
Shen
Ti
T
Zhang
Zhi-nan
ZN
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D018038:Sodium Selenite / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D018038:Sodium Selenite