Methyl-ß-cyclodextrin induces programmed cell death in chronic myeloid leukemia cells and, combined with imatinib, produces a synergistic downregulation of ERK/SPK1 signaling.
Anticancer Drugs
; 23(1): 22-31, 2012 Jan.
Article
en En
| MEDLINE
| ID: mdl-21857502
ABSTRACT
Lipid rafts mediate several survival signals in the development of chronic myeloid leukemia (CML). Methyl-ß-cyclodextrin (MßCD) is an inhibitor specifically designed to disrupt lipid rafts in cells by depleting the cholesterol component. We hypothesize that treatment of CML cells with MßCD and imatinib could reduce imatinib resistance. Apoptotic and autophagic cell death was assayed using annexin V-propidium iodide double staining, immunoblotting, and immunocytochemistry. We next investigated whether MßCD could enhance the cytotoxicity of imatinib in imatinib-sensitive and imatinib-resistant K562 cells. Extracellular signal-regulated kinase/sphingosine kinase 1 signaling downstream of lipid raft-activated signaling pathways was significantly inhibited by treatment of cells with a combination of MßCD and imatinib compared with treatment with either agent alone. MßCD induces programmed cell death in CML cells, and its antileukemia action is synergistic with that of imatinib.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Piperazinas
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Pirimidinas
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Leucemia Mielógena Crónica BCR-ABL Positiva
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Fosfotransferasas (Aceptor de Grupo Alcohol)
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Beta-Ciclodextrinas
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Quinasas MAP Reguladas por Señal Extracelular
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Inhibidores de Proteínas Quinasas
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Antineoplásicos
Límite:
Humans
Idioma:
En
Revista:
Anticancer Drugs
Asunto de la revista:
ANTINEOPLASICOS
Año:
2012
Tipo del documento:
Article