Cytotoxicity of homoharringtonine on leukemic stem-like cells in AML cell line KG-1 / 浙江大学学报·医学版
Journal of Zhejiang University. Medical sciences
; (6): 485-490, 2012.
Artigo
em Chinês
| WPRIM (Pacífico Ocidental)
| ID: wpr-336763
Biblioteca responsável:
WPRO
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the effect of homoharringtonine (HHT) on leukemic stem-like cells (LSC) in human acute myeloid leukemia (AML) cell lines.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>
Texto completo:
Disponível
Base de dados:
WPRIM (Pacífico Ocidental)
Assunto principal:
Patologia
/
Farmacologia
/
Células-Tronco Neoplásicas
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Leucemia Mieloide Aguda
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Regulação Neoplásica da Expressão Gênica
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Apoptose
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Linhagem Celular Tumoral
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Proliferação de Células
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Caspase 3
/
Caspase 9
Limite:
Humanos
Idioma:
Chinês
Revista:
Journal of Zhejiang University. Medical sciences
Ano de publicação:
2012
Tipo de documento:
Artigo