Crown ethers reverse P-glycoprotein-mediated multidrug resistance in cancer cells
Guberovic, Iva (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Marjanović, Marko (Ruđer Bošković Institute. Division of Molecular Medicine)
Mioč, Marija (Ruđer Bošković Institute. Division of Molecular Medicine)
Ester, Katja (Ruđer Bošković Institute. Division of Molecular Medicine)
Martin-Kleiner, Irena (Ruđer Bošković Institute. Division of Molecular Medicine)
Šumanovac Ramljak, Tatjana (Ruđer Bošković Institute. Department of Organic Chemistry and Biochemistry)
Mlinarić-Majerski, Kata (Ruđer Bošković Institute. Department of Organic Chemistry and Biochemistry)
Kralj, Marijeta (Ruđer Bošković Institute. Division of Molecular Medicine)

Data:	2018
Resum:	Multidrug resistance (MDR) is a widespread phenomenon exhibited by many cancers and represents a fundamental obstacle for successful cancer treatments. Tumour cells commonly achieve MDR phenotype through overexpression and/or increased activity of ABC transporters. P-glycoprotein transporter (P-gp, ABCB1) is a major cause of MDR and therefore represents a valuable target for MDR reversal. Several naturally occurring potassium ionophores (e. g. salinomycin) were shown to inhibit P-gp effectively. We have previously shown antitumour activity of a number of 18-crown-6 ether compounds that transport potassium ions across membranes. Here we present data on P-gp inhibitory activity of 16 adamantane-substituted monoaza- and diaza-18-crown-6 ether compounds, and their effect on MDR reversal in model cell lines. We show that crown ether activity depends on their lipophilicity as well as on the linker to adamantane moiety. The most active crown ethers were shown to be more effective in sensitising MDR cells to paclitaxel and adriamycin than verapamil, a well-known P-gp inhibitor. Altogether our data demonstrate a novel use of crown ethers for inhibition of P-gp and reversal of MDR phenotype.
Ajuts:	European Commission 316289
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	Scientific reports, Vol. 8 (september 2018) , ISSN 2045-2322

DOI: 10.1038/s41598-018-32770-y
PMID: 30262858

14 p, 1.7 MB

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Documents de recerca > Documents dels grups de recerca de la UAB > Centres i grups de recerca (producció científica) > Ciències de la salut i biociències > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Institut de Recerca contra la Leucèmia Josep Carreras
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