English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/122080
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:


Circumvention of the multidrug-resistance protein (MRP-1) by an antitumor drug through specific inhibition of gene transcription in breast tumor cells

AuthorsMansilla, Sylvia ; Rojas, Marta; Bataller, Marc ; Priebe, Waldemar; Portugal, José
Issue Date1-Apr-2007
CitationBiochemical Pharmacology 73(7): 934-942 (2007)
AbstractMultidrug-resistance protein 1 (MRP-1) confers resistance to a number of clinically important chemotherapeutic agents. The promoter of the mrp-1 gene contains an Sp1-binding site, which we targeted using the antitumor bis-anthracycline WP631. When MCF-7/VP breast cancer cells, which overexpress MRP-1 protein, were incubated with WP631 the expression of the multidrug-resistance protein gene decreased. Conversely, doxorubicin did not alter mrp-1 gene expression. The inhibition of gene expression was followed by a decrease in the activity of the MRP-1 protein. The IC75 for WP631 (drug concentration required to inhibit cell growth by 75%) circumvented the drug-efflux pump, without addition of resistant modifiers. After treatment with WP631, MCF-7/VP cells were committed to die after entering mitosis (mitotic catastrophe), while treatment with doxorubicin did not affect cell growth. This is the first report on an antitumor drug molecule inhibiting the mrp-1 gene directly, rather than being simply a poor substrate for the transporter-mediated efflux. However, both situations appeared to coexist, thereby a superior cytotoxic effect was attained. Ours results suggest that WP631 offers great potential for the clinical treatment of tumors displaying a multidrug-resistance phenotype. © 2006 Elsevier Inc. All rights reserved.
Publisher version (URL)http://dx.doi.org/10.1016/j.bcp.2006.12.005
Identifiersdoi: 10.1016/j.bcp.2006.12.005
issn: 0006-2952
Appears in Collections:(IBMB) Artículos
Files in This Item:
File Description SizeFormat 
accesoRestringido.pdf15,38 kBAdobe PDFThumbnail
Show full item record
Review this work

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