Carboxyamidotriazole inhibits cell growth of imatinib-resistant chronic myeloid leukaemia cells including T315I Bcr-Abl mutant by a redox-mediated mechanism.
Cancer Lett
; 300(2): 205-14, 2011 Jan 28.
Article
en En
| MEDLINE
| ID: mdl-21041018
ABSTRACT
Mutation of the Bcr-Abl oncoprotein is one of most frequent mechanisms by which chronic myelogenous leukemia (CML) cells become resistant to imatinib. Here, we show that treatment of cell lines harbouring wild type or mutant BCR-ABL with carboxyamidotriazole (CAI), a calcium influx and signal transduction inhibitor, inhibits cell growth, the expression of Bcr-Abl and its downstream signalling, and induces apoptosis. Moreover, we show that CAI acts by increasing intracellular ROS. Clinically significant, CAI has also inhibitory effects on T315I Bcr-Abl mutant, a mutation that causes CML cells to become insensitive to imatinib and second generation abl kinase inhibitors.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Oxidación-Reducción
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Triazoles
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Leucemia Mielógena Crónica BCR-ABL Positiva
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Proteínas de Fusión bcr-abl
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Antineoplásicos
Límite:
Animals
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Humans
Idioma:
En
Revista:
Cancer Lett
Año:
2011
Tipo del documento:
Article
País de afiliación:
Italia