English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/123251
Share/Impact:
Statistics
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 | DATACITE
Exportar a otros formatos:

Title

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

AuthorsPera, 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.
KeywordsMicrotubules
Leukemia
Resistance
Chemotherapy
AML
P-glycopro
Issue Date1-Nov-2015
PublisherElsevier
CitationCancer Letters 368 (1) 97–104 (2015)
AbstractTreatment 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.
Description16 p.-5 fig.-1 tab.-1 fig. supl.
Publisher version (URL)http://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
Appears in Collections:(CIB) Artículos
Files in This Item:
File Description SizeFormat 
Pera et al 2015.pdfPostprint193,38 kBAdobe PDFThumbnail
View/Open
Pera et al 2015_Figures.pdfFiguras4,88 MBAdobe PDFThumbnail
View/Open
Show full item record
Review this work
 

Related articles:


WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.