Abstract |
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.
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Authors | Bingshe Han, Yun Ren, Liying Guan, Wei Wei, Fangyuan Hua, Yang Yang, Tao Yang, Tingming Cao, Hua Dong, Huazhen Pan, Caimin Xu |
Journal | Oncology research
(Oncol Res)
Vol. 17
Issue 8
Pg. 373-81
( 2009)
ISSN: 0965-0407 [Print] United States |
PMID | 19544974
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents
- RNA, Small Interfering
- Reactive Oxygen Species
- bcl-2-Associated X Protein
- bcl-Associated Death Protein
- Cytochromes c
- Caspases
- Sodium Selenite
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Topics |
- Antineoplastic Agents
(pharmacology)
- Apoptosis
(drug effects, physiology)
- Blotting, Western
- Caspases
(drug effects, metabolism)
- Cell Line, Tumor
- Cytochromes c
(drug effects, metabolism)
- Flow Cytometry
- Humans
- Immunoprecipitation
- Leukemia, Promyelocytic, Acute
(metabolism, pathology)
- Membrane Potential, Mitochondrial
(drug effects)
- Mitochondria
(drug effects)
- RNA, Small Interfering
- Reactive Oxygen Species
(metabolism)
- Signal Transduction
(drug effects, physiology)
- Sodium Selenite
(pharmacology)
- bcl-2-Associated X Protein
(drug effects, metabolism)
- bcl-Associated Death Protein
(drug effects, metabolism)
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