Document Detail


Reversal of multidrug resistance in murine lymphoma cells by amphiphilic dihydropyridine antioxidant derivative.
MedLine Citation:
PMID:  21036720     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Multidrug resistance, the principal mechanism by which cancer cells develop resistance to chemotherapy drugs, is a major factor in the failure of many forms of chemotherapies.
AIM: The aim of the study was to investigate the effect of K-2-11 on the reversal of multidrug resistance.
MATERIALS AND METHODS: The effects of amphiphilic dihydropyridine derivative K-2-11 were tested on MDR1-expressing mouse lymphoma cells and their parental control. The effects of K-2-11 with and without doxorubicin were studied by determination of cell viability, cell proliferation and production of reactive oxygen species.
RESULTS: K-2-11 caused complete reversal of multidrug resistance of the MDR cells, being much more efficient than the positive control verapamil. Accordingly, the cytotoxic effects of doxorubicin were enhanced by K-2-11, both in the MDR and in parental cell line, while K-2-11 alone did not affect cell viability. K-2-11 also acted as an antioxidant, reducing the cellular generation of reactive oxygen species.
CONCLUSION: Our results indicate the high potential of K-2-11 as a novel antioxidant with potent MDR-blocking ability that should be studied further for development in adjuvant anticancer treatments.
Authors:
Marina Cindric; Ana Cipak; Julianna Serly; Aiva Plotniece; Morana Jaganjac; Lidija Mrakovcic; Tomislava Lovakovic; Azra Dedic; Ivo Soldo; Gunars Duburs; Neven Zarkovic; József Molnár
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Anticancer research     Volume:  30     ISSN:  1791-7530     ISO Abbreviation:  Anticancer Res.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-11-01     Completed Date:  2010-12-10     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8102988     Medline TA:  Anticancer Res     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  4063-9     Citation Subset:  IM    
Affiliation:
Department of Pathology, School of Medicine, University of Zagreb, Zagreb, Croatia.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antioxidants / pharmacology*
Dihydropyridines / pharmacology*
Doxorubicin / pharmacology
Drug Resistance, Multiple
Drug Resistance, Neoplasm
Drug Synergism
Humans
Leukemia L5178
Lymphoma, T-Cell / drug therapy*,  genetics,  metabolism
Mice
P-Glycoprotein / genetics
Reactive Oxygen Species / metabolism
Transfection
Chemical
Reg. No./Substance:
0/ABCB1 protein, human; 0/Antioxidants; 0/Dihydropyridines; 0/K-2-11 compound; 0/P-Glycoprotein; 0/Reactive Oxygen Species; 23214-92-8/Doxorubicin

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