Tetraarsenic Hexoxide Induces Beclin-1-Induced Autophagic Cell Death as well as Caspase-Dependent Apoptosis in U937 Human Leukemic Cells

被引:9
作者
Han, Min Ho [1 ,2 ]
Lee, Won Sup [3 ,4 ]
Lu, Jing Nan [3 ]
Yun, Jeong Won [3 ]
Kim, GonSup [5 ,6 ]
Jung, Jin Myung [7 ]
Kim, Gi-Young [8 ]
Lee, Su-Jae [9 ]
Kim, Wun-Jae [10 ]
Choi, Yung Hyun [1 ,2 ]
机构
[1] Dong Eui Univ, Coll Oriental Med, Dept Biochem, Pusan 614052, South Korea
[2] Dong Eui Univ, Grad Sch, Program BK21, Dept Biomat Control, Pusan 614052, South Korea
[3] Gyeongsang Natl Univ, Dept Internal Med, Inst Hlth Sci, Sch Med, Jinju 660702, South Korea
[4] Gyeongsang Natl Univ, Sch Med, Gyeongnam Reg Canc Ctr, Jinju 660702, South Korea
[5] Gyeongsang Natl Univ, Sch Vet Med, Jinju 660701, South Korea
[6] Gyeongsang Natl Univ, Inst Life Sci, Jinju 660701, South Korea
[7] Gyeongsang Natl Univ, Sch Med, Inst Hlth Sci, Dept Neurosurg, Jinju 660702, South Korea
[8] Jeju Natl Univ, Dept Marine Life Sci, Immunobiol Lab, Cheju 690756, South Korea
[9] Hanyang Univ, Dept Chem, Seoul 133, South Korea
[10] Chungbuk Natl Univ, Coll Med, Dept Urol, Cheongju 361763, Chungbuk, South Korea
基金
新加坡国家研究基金会;
关键词
ACUTE PROMYELOCYTIC LEUKEMIA; ARSENIC TRIOXIDE AS2O3; MALIGNANT GLIOMA-CELLS; DOWN-REGULATION; GROWTH-INHIBITION; MODULATION; INDUCTION; EXPRESSION; MECHANISM; RELEASE;
D O I
10.1155/2012/201414
中图分类号
R [医药、卫生];
学科分类号
10 ;
摘要
Tetraarsenic hexaoxide (As4O6) has been used in Korean folk remedy for the treatment of cancer since the late 1980s, and arsenic trioxide (As2O3) is currently used as a chemotherapeutic agent. However, evidence suggests that As4O6-induced cell death pathway was different from that of As2O3. Besides, the anticancer effects and mechanisms of As4O6 are not fully understood. Therefore, we investigated the anticancer activities of As4O6 on apoptosis and autophagy in U937 human leukemic cells. The growth of U937 cells was inhibited by As4O6 treatment in a dose-and a time-dependent manner, and IC50 for As4O6 was less than 2 mu M. As4O6 induced caspase-dependent apoptosis and Beclin-1-induced autophagy, both of which were significantly attenuated by Bcl-2 augmentation and N-acetylcysteine (NAC) treatment. This study suggests that As4O6 should induce Beclin-1-induced autophagic cell death as well as caspase-dependent apoptosis and that it might be a promising agent for the treatment of leukemia.
引用
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页数:11
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