Title
Reversal of in vitro cellular MRP1 and MRP2 mediated vincristine resistance by the flavonoid myricetin
Author
van Zanden, J.J.
de Mul, A.
Wortelboer, H.M.
Usta, M.
van Bladeren, P.J.
Rietjens, I.M.C.M.
Cnubben, N.H.P.
TNO Kwaliteit van Leven
Publication year
2005
Abstract
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 μM for MRP1 and 24.6 ± 1.3 μM 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 μM. 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 μM, respectively. In both the MRP1 and MRP2 cells, exposure to 25 μM myricetin enhances the sensitivity of the cells towards vincristine toxicity to IC50 values of 7.6 ± 0.5 and 5.8 ± 0.5 μM, 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. © 2005 Elsevier Inc. All rights reserved.
Subject
Biology
Physiological Sciences
Flavonoids
MRP1
MRP2
Multidrug resistance
Myricetin
Vincristine
antineoplastic agent
flavonoid
multidrug resistance protein 1
multidrug resistance protein 2
myricetin
vincristine
animal cell
article
cell line
cell proliferation
chemotherapy
concentration (parameters)
controlled study
drug resistance
drug transport
genetic transfection
IC 50
in vitro study
nonhuman
priority journal
Animals
Cell Line
Cell Proliferation
Dogs
Dose-Response Relationship, Drug
Drug Resistance, Neoplasm
Flavonoids
Humans
Membrane Transport Modulators
Membrane Transport Proteins
Multidrug Resistance-Associated Proteins
Vincristine
To reference this document use:
http://resolver.tudelft.nl/uuid:5f97a9ba-e653-428f-962d-4bb521263bef
DOI
https://doi.org/10.1016/j.bcp.2005.03.001
TNO identifier
238540
ISSN
0006-2952
Source
Biochemical Pharmacology, 69 (11), 1657-1665
Document type
article