Document Detail

8-Prenylnaringenin is an inhibitor of multidrug resistance-associated transporters, P-glycoprotein and MRP1.
MedLine Citation:
PMID:  20633549     Owner:  NLM     Status:  MEDLINE    
Flavonoids with hydrophobic e.g. prenyl substituents might constitute the promising candidates for multidrug resistance (MDR) reversal agents. The interaction of 8-prenylnaringenin (8-isopentenylnaringenin), a potent phytoestrogen isolated from common hop (Humulus lupulus), with two multidrug resistance-associated ABC transporters of cancer cells, P-glycoprotein and MRP1, has been studied for the first time. Functional test based on the transport of fluorescent substrate BCECF revealed that the flavonoid strongly inhibited MRP1 transport activity in human erythrocytes (IC(50)=5.76+/-1.80muM). Expression of MDR-related transporters in drug-sensitive (LoVo) and doxorubicin-resistant (LoVo/Dx) human colon adenocarcinoma cell lines was characterized by RT-PCR and immunochemical methods and elevated expression of P-glycoprotein in resistant cells was found to be the main difference between these two cell lines. By means of flow cytometry it was shown that 8-prenylnaringenin significantly increased the accumulation of rhodamine 123 in LoVo/Dx cells. Doxorubicin accumulation in both LoVo and LoVo/Dx cells observed by confocal microscopy was also altered in the presence of 8-prenylnaringenin. However, the presence of the studied compound did not increase doxorubicin cytotoxicity to LoVo/Dx cells. It was concluded that 8-prenylnaringenin was not able to modulate MDR in human adenocarcinoma cell line in spite of the ability to inhibit both P-glycoprotein and MRP1 activities. To our best knowledge, this is the first report of 8-prenylnaringenin interaction with clinically important ABC transporters.
Olga Wesołowska; Jerzy Wiśniewski; Kamila Sroda; Agnieszka Krawczenko; Aleksandra Bielawska-Pohl; Maria Paprocka; Danuta Duś; Krystyna Michalak
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-07-13
Journal Detail:
Title:  European journal of pharmacology     Volume:  644     ISSN:  1879-0712     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-08-17     Completed Date:  2010-12-07     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  32-40     Citation Subset:  IM    
Copyright Information:
Copyright 2010 Elsevier B.V. All rights reserved.
Department of Biophysics, Wrocław Medical University, ul. Chałubińskiego 10, 50-368 Wrocław, Poland.
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MeSH Terms
Adenocarcinoma / drug therapy,  pathology
Antibiotics, Antineoplastic / pharmacology
Cell Line, Tumor
Colonic Neoplasms / drug therapy,  pathology
Doxorubicin / pharmacology*
Drug Resistance, Neoplasm
Erythrocytes / drug effects,  metabolism
Flavanones / isolation & purification,  pharmacology*
Flow Cytometry
Humulus / chemistry
Inhibitory Concentration 50
Multidrug Resistance-Associated Proteins / antagonists & inhibitors*,  metabolism
P-Glycoprotein / antagonists & inhibitors*,  metabolism
Phytoestrogens / isolation & purification,  pharmacology
Reverse Transcriptase Polymerase Chain Reaction
Reg. No./Substance:
0/8-prenylnaringenin; 0/Antibiotics, Antineoplastic; 0/Flavanones; 0/Multidrug Resistance-Associated Proteins; 0/P-Glycoprotein; 0/Phytoestrogens; 0/multidrug resistance-associated protein 1; 23214-92-8/Doxorubicin

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