Celastrol Induces Cell Apoptosis and Inhibits the Expression of the AML1-ETO/C-KIT Oncoprotein in t(8;21) Leukemia

被引：24
作者：
Yu, Xianjun [1 ,2 ,3 ]
Ruan, Xuzhi [1 ]
Zhang, Jingxuan [1 ]
Zhao, Qun [2 ]
机构：
[1] Hubei Univ Med, Sch Basic Med Sci, Shiyan 442000, Peoples R China
[2] Chinese Acad Sci, Shanghai Inst Biol Sci, Key Lab Nutr & Metab, Inst Nutr Sci,Grad Sci, Shanghai 200031, Peoples R China
[3] Hubei Univ Med, Renmin Hosp, Ctr Oncol, Lab Chinese Herbal Pharmacol, Shiyan 442000, Peoples R China
来源：
MOLECULES | 2016年 / 21卷 / 05期
基金：
中国国家自然科学基金;
关键词：
celastrol; t(8; 21) leukemia; apoptosis; mitochondrial dysfunction; C-KIT; ACUTE MYELOID-LEUKEMIA; LUNG-CANCER CELLS; C-KIT; OXIDATIVE STRESS; DOWN-REGULATION; DEGRADATION; DEATH; MUTATIONS; PATHWAYS; GROWTH;
D O I：
10.3390/molecules21050574
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Resistance to chemotherapy is a major challenge to improving overall survival in Acute Myeloid Leukemia (AML). Therefore, the development of innovative therapies and the identification of more novel agents for AML are urgently needed. Celastrol, a compound extracted from the Chinese herb Tripterygium wilfordii Hook, exerts anticancer activity. We investigated the effect of celastrol in the t(8;21) AML cell lines Kasumi-1 and SKNO-1. We demonstrated that inhibition of cell proliferation activated caspases and disrupted mitochondrial function. In addition, we found that celastrol downregulated the AML1-ETO fusion protein, therefore downregulating C-KIT kinases and inhibiting AKT, STAT3 and Erk1/ 2. These findings provide clear evidence that celastrol might provide clinical benefits to patients with t(8;21) leukemia.
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页数：11
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