Document Detail


Reversal of in vitro cellular MRP1 and MRP2 mediated vincristine resistance by the flavonoid myricetin.
MedLine Citation:
PMID:  15896345     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In the present study, the effects of myricetin on either MRP1 or MRP2 mediated vincristine resistance in transfected MDCKII cells were examined. The results obtained show that myricetin can inhibit both MRP1 and MRP2 mediated vincristine efflux in a concentration dependent manner. The IC50 values for cellular vincristine transport inhibition by myricetin were 30.5+/-1.7 microM for MRP1 and 24.6+/-1.3 microM for MRP2 containing MDCKII cells. Cell proliferation analysis showed that the MDCKII control cells are very sensitive towards vincristine toxicity with an IC50 value of 1.1+/-0.1 microM. The MDCKII MRP1 and MRP2 cells are less sensitive towards vincristine toxicity with IC50 values of 33.1+/-1.9 and 22.2+/-1.4 microM, respectively. In both the MRP1 and MRP2 cells, exposure to 25 microM myricetin enhances the sensitivity of the cells towards vincristine toxicity to IC50 values of 7.6+/-0.5 and 5.8+/-0.5 microM, respectively. The increase of sensitivity represents a reversal of the resistance towards vincristine as a result of MRP1 and MRP2 inhibition. Thus, the present study demonstrates the ability of the flavonoid myricetin to modulate MRP1 and MRP2 mediated resistance to the anticancer drug vincristine in transfected cells, indicating that flavonoids might be a valuable adjunct to chemotherapy to block MRP mediated resistance.
Authors:
Jelmer J van Zanden; Anika de Mul; Heleen M Wortelboer; Mustafa Usta; Peter J van Bladeren; Ivonne M C M Rietjens; Nicole H P Cnubben
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2005-04-13
Journal Detail:
Title:  Biochemical pharmacology     Volume:  69     ISSN:  0006-2952     ISO Abbreviation:  Biochem. Pharmacol.     Publication Date:  2005 Jun 
Date Detail:
Created Date:  2005-05-17     Completed Date:  2005-07-08     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0101032     Medline TA:  Biochem Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1657-65     Citation Subset:  IM    
Affiliation:
Division of Toxicology, Wageningen University, P.O. Box 8000, 6700 EA, Wageningen, The Netherlands. Jelmer.vanZanden@wur.nl
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Line
Cell Proliferation / drug effects
Dogs
Dose-Response Relationship, Drug
Drug Resistance, Neoplasm / drug effects*,  physiology
Flavonoids / chemistry,  metabolism,  pharmacology*
Humans
Membrane Transport Modulators
Membrane Transport Proteins / antagonists & inhibitors,  physiology*
Multidrug Resistance-Associated Proteins / antagonists & inhibitors,  physiology*
Vincristine / metabolism,  pharmacology*
Chemical
Reg. No./Substance:
0/Flavonoids; 0/Membrane Transport Modulators; 0/Membrane Transport Proteins; 0/Multidrug Resistance-Associated Proteins; 0/multidrug resistance-associated protein 1; 0/multidrug resistance-associated protein 2; 529-44-2/myricetin; 57-22-7/Vincristine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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