Autophagy inhibition through PI3K/Akt increases apoptosis by sodium selenite in NB4 cells.
Selenium possesses the chemotherapeutic feature by inducing apoptosis in cancer cell with trivial side effects on normal cells. However, the mechanism in which is not clearly understood. Emerging evidence indicates the overlaps between the autophagy and the apoptosis. In this study, we have investigated the role of autophagy in selenium-induced apoptosis in NB4 cells. We find that autophagy is suppressed in NB4 cells treated by sodium selenite, as measured by electron microscope, acridine orange staining and western blot. Moreover, selenite combined with autophagy inhibitor contributes to the up-regulation of apoptosis, while the PI3K/Akt signaling pathway is down- regulated. Consistently, when the inhibitor of PI3K was applied, the autophagic level significantly decreased. In summary, sodium selenite increases NB4 cell apoptosis by autophagy inhibition through PI3K/Akt, and the inhibition of autophagy contributes to the up-regulation of apoptosis. [BMB reports 2009; 42(9): 599-604].
Ren
Yun
Y
National Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Science, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
Huang
Fang
F
Liu
Yuan
Y
Yang
Yang
Y
Jiang
Qian
Q
Xu
Caimin
C
D000165:Acridine Orange; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy; D015153:Blotting, Western; D002867:Chromones / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018038:Sodium Selenite / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000165:Acridine Orange; D002867:Chromones; D004791:Enzyme Inhibitors; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D018038:Sodium Selenite; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one