The microtubule depolymerizing agent CYT997 effectively kills acute myeloid leukemia cells via activation of caspases and inhibition of PI3K/Akt/mTOR pathway proteins

被引：20

作者：

Chen, Xiaohui ^{[1
]}

Yang, Chunmei ^{[2
]}

Xu, Yanhua ^{[2
]}

Zhou, Hui ^{[1
]}

Liu, Hui ^{[2
]}

Qian, Wenbin ^{[2
]}

机构：

[1] Hangzhou Normal Univ, Affiliated Hosp, Dept Hematol, Hangzhou 310015, Zhejiang, Peoples R China

[2] Zhejiang Univ, Coll Med, Affiliated Hosp 1, Inst Hematol, Hangzhou 310003, Zhejiang, Peoples R China

来源：

EXPERIMENTAL AND THERAPEUTIC MEDICINE | 2013年 / 6卷 / 02期

基金：

中国国家自然科学基金;

关键词：

CYT997; apoptosis; acute myeloid leukemia; VASCULAR-DISRUPTING AGENT; TARGETING AGENT; PHASE-I; VIVO;

D O I：

10.3892/etm.2013.1161

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

The orally active microtubule-depolymerizing agent CYT997 is potently cytotoxic to a variety of tumors in vitro and in vivo. However, the effects of this agent on acute myeloid leukemia (AML) cells and its mechanisms are unknown. The present study demonstrated that CYT997 effectively inhibited the growth of AML cells in vitro. Treatment of AML cells with CYT997 resulted in G2/M phase cell cycle arrest, and induced apoptosis through the activation of extrinsic and intrinsic apoptotic pathways. Furthermore, CYT997 induced cell death in CD123(+) leukemia cells and significantly reduced leukemia colony formation. CYT997 was also demonstrated to exert dual effects on the expression of PI3K/Akt and mechanistic target of rampamycin (mTOR) signaling pathway proteins. Therefore, CTY997, used alone or in combination with chemotherapy, may represent a promising approach for the treatment of AML.

引用

页码：299 / 304

页数：6

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