ITF-2357 on inhibition myeloid leukemic cell lines cells proliferation in vitro and its mechanism / 中华血液学杂志
Chinese Journal of Hematology
; (12): 366-370, 2012.
Artículo
en Chino
| WPRIM (Pacífico Occidental)
| ID: wpr-359482
Biblioteca responsable:
WPRO
ABSTRACT
<p><b>OBJECTIVE</b>To explore the effect of ITF2357, a novel histone deacetylase (HDAC) inhibitor, on the growth, differentiation and apoptosis of acute myeloid leukemic (AML) cells and its mechanism.</p><p><b>METHODS</b>AML cell lines kasumi-1 cells as a model for AML1-ETO positive, and THP1 cells for AML1-ETO negative, the leukemic cells proliferation was analyzed by MTT assay, expression of myeloid-specific differentiation antigen and cell cycle by flow cytometry, cell apoptosis by annexin V staining and flow cytometry. AML1-ETO, acetyl-histone, and caspase protein was analyzed by Western blot.</p><p><b>RESULTS</b>0.5 µmol/L ITF2357 treatment significantly inhibited kasumi-1 cells proliferation, with the 48 h half inhibitory concentration (IC(50)) of 0.1 µmol/L. The initial inhibitory concentration of THP1 cell line was 5 µmol/L. ITF 2357 induced apoptosis of kasumi-1 cells in a time- and dose-dependent manner. A dose-dependent increase in early apoptosis occurred at 24 hours treatment and in late apoptosis at 48 hours treatment by ITF2357. Early apoptosis cells increased from (1.44 ± 1.52)% to (24.51 ± 5.79)%. Late apoptosis cells increased from (2.37 ± 2.8)% to (63.66 ± 1.56)%. ITF2357 induced AML1-ETO degradation by caspase-dependent pathway. 0.25 µmol/L ITF2357 induced a time- and dose-dependent increase in expression of myeloid cell surface protein CD13 and CD15. 5 µmol/L ITF2357 blocked the cells at G(0)/G(1) phase, G(0)/G(1) cells increased from (39.69 ± 6.56)% to (79.2 ± 6.51)% and s-phase cells declined from (60.12 ± 3.29)% to (18.97 ± 6.62)%. Kasumi-1 cells incubated with 0.5 µmol/L of ITF2357, AML1-ETO protein began to decrease at 24 hours and could hardly be detected at 96 hours. ITF2357 induced AML1/ETO degradation through a caspase-dependent mechanism. At the same time, acetylated H3 and H4 increased.</p><p><b>CONCLUSION</b>Low-dose HDAC inhibitor ITF2357 can effectively inhibit the AML cells proliferation, especially for AML1-ETO positive AML cells. It inhibits Kasumi-1 cells proliferation degradation of AML1-ETO protein expression, blocks the cells at G(0)/G(1) phase, and induces apoptosis and differentiation of the cells.</p>
Texto completo:
Disponible
Contexto en salud:
ODS3 - Meta 3.4 Reducir las muertes prematuras por enfermedades no transmisibles
Problema de salud:
Leucemia
Base de datos:
WPRIM (Pacífico Occidental)
Asunto principal:
Farmacología
/
Acetilación
/
Histonas
/
Proteínas de Fusión Oncogénica
/
Diferenciación Celular
/
Apoptosis
/
Línea Celular Tumoral
/
Proliferación Celular
/
Inhibidores de Histona Desacetilasas
/
Ácidos Hidroxámicos
Límite:
Humanos
Idioma:
Chino
Revista:
Chinese Journal of Hematology
Año:
2012
Tipo del documento:
Artículo