Killing effect of aurora kinase inhibitor ENMD-2076 on acute myelogenous leukemia cells.
- Author:
Hui CAO
1
;
Min LI
;
Wen-bin QIAN
Author Information
- Publication Type:Journal Article
- MeSH: Apoptosis; drug effects; Apoptosis Regulatory Proteins; metabolism; Aurora Kinases; Caspases; metabolism; Cell Line, Tumor; Cell Proliferation; drug effects; Humans; Leukemia, Myeloid, Acute; metabolism; pathology; Protein-Serine-Threonine Kinases; antagonists & inhibitors; Pyrazoles; pharmacology; Pyrimidines; pharmacology
- From: Journal of Zhejiang University. Medical sciences 2012;41(5):479-484
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the effect of aurora kinase inhibitor ENMD-2076 on human acute myelogenous leukemia (AML) cell lines.
METHODSAML THP-1 and Kasumi-1 cells were treated with ENMD-2076 for 24 h and 48 h,respectively. Cell growth was measured by MTT assay. Apoptosis was determined using Hoechst staining apoptosis detection kit. Activation of Caspase pathway and expression of apoptosis regulator proteins were detected by Western blot.
RESULTSENMD-2076 significantly induced growth arrest and apoptosis in THP-1 and Kasumi-1 cells. Enhanced apoptosis was observed in ENMD-2076 group evidenced by strong activation of Caspase-9,Caspase-3 and PARP. Furthermore,the ENMD-2076 treatment resulted in down-regulation of anti-apoptotic protein Mcl-1 expression. Also,up-regulated expression of pro-apoptotic protein Bak,Bad and Bax was detected after ENMD-2076 treatment.
CONCLUSIONENMD-2076 can kill effectively AML cells by inhibiting cell growth and inducing apoptosis,which is associated with activation of Caspase pathway and regulation of pro-apoptotic and anti-apoptotic proteins.
