English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/67203
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

AT514, a cyclic depsipeptide from Serratia marcescens, induces apoptosis of B-chronic lymphocytic leukemia cells. Interference with the Akt/NF-kB survival pathway

AuthorsEscobar-Díaz, Elisabeth; López-Martín, E.M.; Hernández del Cerro, Mercedes CSIC; Puig-Kröger, Amaya CSIC; Soto-Cerrato, V.; Montaner, B.; Giralt, Ernest; García-Marco, José A.; Pérez-Tomás, R.; García-Pardo, Angeles CSIC ORCID
KeywordsB-CLL
apoptosis
depsipeptide
caspase activation
Akt/NF-B pathway
Issue DateApr-2005
PublisherNature Publishing Group
CitationLeukemia, 19 (4) : 572-579 (2005)
AbstractClinical treatment of B-cell chronic lymphocytic leukemia (B-CLL) is limited by the progressive drug resistance and nonselectivity of most drugs towards malignant cells. Depsipeptides are present in certain bacteria and display potent antitumor activity. We have studied the effect of the novel cyclodepsipeptide AT514 (serratamolide) from Serratia marcescens on B-CLL cell viability. AT514 induced apoptosis of B-CLL cells from the 21 patients studied, as confirmed by Annexin-V binding and nuclei condensation, with an average IC50 of 13 M. AT514 was effective in those B-CLL cases resistant to fludarabine, but had no effect on normal PBL. AT514 preferentially activated the intrinsic apoptotic pathway, as evidenced by loss of mitochondrial membrane potential, release of cytochrome c and activation of caspase-9 and -3, but not of caspase-8. Importantly, AT514 interfered with phosphatidylinositol-3 kinase and protein kinase C survival signals since it increased the apoptotic effect of LY294002 and BisI inhibitors, and induced Akt dephosphorylation at Ser 473. AT514 also decreased NF-B activity by dramatically reducing the levels of p65 in B-CLL. This was confirmed on functional assays using NF-B-luc-transfected Raji cells and transgenic mice. Our results establish that AT514 induces apoptosis of primary B-CLL cells and could be useful for clinical treatment of this malignancy
Description8 páginas, 5 figuras -- PAGS nros. 572-579
Publisher version (URL)http://dx.doi.org/10.1038/sj.leu.2403679
URIhttp://hdl.handle.net/10261/67203
DOIhttp://dx.doi.org/10.1038/sj.leu.2403679
ISSN0887-6924
E-ISSN1476-5551
Appears in Collections:(CIB) Artículos
Files in This Item:
File Description SizeFormat 
restringido.pdf21,67 kBAdobe 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.