Sodium selenite induces apoptosis in acute promyelocytic leukemia-derived NB4 cells through mitochondria-dependent pathway.
Our previous study has shown that sodium selenite can cause apoptosis in acute promyelocytic leukemia-derived NB4 cells in a caspase-dependent manner involving Deltapsim disruption and cleavage of Bcl-2, but more detailed mechanism(s) remain unclear. Here we showed that mitochondrial apoptosis signaling pathway played a vital role in apoptosis induced by sodium selenite based on the following findings: 1) cytochrome c release, activation of caspase 9, mitochondrial targeting, and oligermerization of Bax; 2) caspase 9, but not caspase 8, inhibitor could attenuate apoptosis; 3) downregulation of Bax and Bad by siRNA could delay sodium selenite-induced apoptosis. Further investigation showed that ROS was an essential inducer of deltapsim disruption and apoptosis by sodium selenite. Our findings here demonstrate that sodium selenite can induce apoptosis in NB4 cells through a mechanism involving ROS, activation of proapoptotic proteins Bad and Bax, Deltapsim disruption, release of cytochrome c, and consequent initiation of caspase cascade.
Han
Bingshe
B
National Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
Ren
Yun
Y
Guan
Liying
L
Wei
Wei
W
Hua
Fangyuan
F
Yang
Yang
Y
Yang
Tao
T
Cao
Tingming
T
Dong
Hua
H
Pan
Huazhen
H
Xu
Caimin
C
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D015153:Blotting, Western; D020169:Caspases / Q000187:drug effects / Q000378:metabolism; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000187:drug effects / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D047468:Immunoprecipitation; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism* / Q000473:pathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects*; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D018038:Sodium Selenite / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000187:drug effects / Q000378:metabolism; D051025:bcl-Associated Death Protein / Q000187:drug effects / Q000378:metabolism
D000970:Antineoplastic Agents; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein; D045304:Cytochromes c; D020169:Caspases; D018038:Sodium Selenite