Cytotoxicity of homoharringtonine on leukemic stem-like cells in AML cell line KG-1.
- Author:
Jian-ping SHEN
1
;
Hong YANG
;
Wan-mao NI
;
Wen-bin QIAN
Author Information
- Publication Type:Journal Article
- MeSH: Antineoplastic Agents, Phytogenic; pharmacology; Apoptosis; drug effects; Caspase 3; metabolism; Caspase 9; metabolism; Cell Line, Tumor; Cell Proliferation; drug effects; Gene Expression Regulation, Neoplastic; Harringtonines; pharmacology; Humans; Leukemia, Myeloid, Acute; metabolism; pathology; Neoplastic Stem Cells; drug effects; metabolism; pathology
- From: Journal of Zhejiang University. Medical sciences 2012;41(5):485-490
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the effect of homoharringtonine (HHT) on leukemic stem-like cells (LSC) in human acute myeloid leukemia (AML) cell lines.
METHODSThe phenotypes of AML cell lines U937,Kasumi-1,and KG-1 cells were analyzed by flow cytometry (FACS). The effect of HHT on leukemia stem-like cells with immunophenotype of CD34(+)CD38(-)CD96(+) was detected with FACS. Cell growth was measured by MTT assay. Activation of Caspase pathway and expression of apoptosis-related regulator proteins were examined by Western blotting.
RESULTSFACS demonstrated that the 69% of KG-1 cells expressed LSC phenotype CD34(+)CD38(-)CD96(+), while 26.7% on Kasumi-1 cells expressed this marker. In contrast,U937 cells showed CD96 negative. HHT significantly inhibited cell growth of KG-1 cells with an IC(50) of 16.9 ng/ml at 48 h. The ratio of CD34(+)CD38(-)CD96(+) cells decreased from 63.6% to 17.1% after HHT treatment. Enhanced apoptosis was demonstrated in HHT group evidenced by strong activation of Caspase-9,Caspase-3 and PARP.HHT treatment resulted in down-regulation of expression of anti-apoptotic protein BCL-2 and phosphorylated-Akt.
CONCLUSIONHHT can effectively kill the leukemic stem-like cells in human AML cell line KG1 by inhibiting cell growth and inducing apoptosis which is associated with activation of Caspase pathway and down-regulation of anti-apoptotic proteins and phosphorylated-Akt.
