English   español  
Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/123251
COMPARTIR / IMPACTO:
Estadísticas
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:
Título

High affinity and covalent-binding microtubule stabilizing agents show activity in chemotherapy-resistant acute myeloid leukemia cells

AutorPera, Benet ; Calvo, María Nieves; Ambati, Srikanth; Jordi, Michel; Kahn, Alissa; Díaz, José Fernando ; Fang, Wei-shuo S.; Altmann, Karl-Heinz; Cerchietti, ,Leandro; Moore, Malcolm A. S.
Palabras claveMicrotubules
Leukemia
Resistance
Chemotherapy
AML
P-glycopro
Fecha de publicación1-nov-2015
EditorElsevier
CitaciónCancer Letters 368 (1) 97–104 (2015)
ResumenTreatment failure in acute myeloid leukemia (AML) is frequently due to the persistence of a cell population resistant to chemotherapy through different mechanisms, in which drug efflux via ATP-binding cassette (ABC) proteins, specifically P-glycoprotein, is one of the most recognized. However, disappointing results from clinical trials employing inhibitors for these transporters have demonstrated the need to adopt different strategies. We hypothesized that microtubule targeting compounds presenting high affinity or covalent binding could overcome the effect of ABC transporters. We therefore evaluated the activity of the high-affinity paclitaxel analog CTX-40 as well as the covalent binder zampanolide (ZMP) in AML cells. Both molecules were active in chemosensitive as well as in chemoresistant cell lines overexpressing P-glycoprotein. Moreover, ZMP or CTX-40 in combination with daunorubicin showed synergistic killing without increased in vitro hematopoietic toxicity. In a primary AML sample, we further demonstrated that ZMP and CTX-40 are active in progenitor and differentiated leukemia cell populations. In sum, our data indicate that high affinity and covalent-binding anti-microtubule agents are active in AML cells otherwise chemotherapy resistant.
Descripción16 p.-5 fig.-1 tab.-1 fig. supl.
Versión del editorhttp://dx.doi.org/ 10.1016/j.canlet.2015.07.038
URIhttp://hdl.handle.net/10261/123251
DOI10.1016/j.canlet.2015.07.038
ISSN0304-3835
E-ISSN1872-7980
Aparece en las colecciones: (CIB) Artículos
Ficheros en este ítem:
Fichero Descripción Tamaño Formato  
Pera et al 2015.pdfPostprint193,38 kBAdobe PDFVista previa
Visualizar/Abrir
Pera et al 2015_Figures.pdfFiguras4,88 MBAdobe PDFVista previa
Visualizar/Abrir
Mostrar el registro completo
 

Artículos relacionados:


NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.