[Cytotoxicity of homoharringtonine on leukemic stem-like cells in AML cell line KG-1].
Zhejiang Da Xue Xue Bao Yi Xue Ban
; 41(5): 485-90, 2012 Sep.
Article
en Zh
| MEDLINE
| ID: mdl-23086639
ABSTRACT
OBJECTIVE:
To investigate the effect of homoharringtonine (HHT) on leukemic stem-like cells (LSC) in human acute myeloid leukemia (AML) cell lines.METHODS:
The 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.RESULTS:
FACS 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.CONCLUSION:
HHT 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.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Células Madre Neoplásicas
/
Leucemia Mieloide Aguda
/
Harringtoninas
/
Antineoplásicos Fitogénicos
Límite:
Humans
Idioma:
Zh
Revista:
Zhejiang Da Xue Xue Bao Yi Xue Ban
Asunto de la revista:
MEDICINA
Año:
2012
Tipo del documento:
Article
País de afiliación:
China