Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.ejps.2008.06.001
Title: Modulation of breast cancer resistance protein (BCRP/ABCG2) by non-basic chalcone analogues
Authors: Han, Y. 
Riwanto, M.
Go, M.-L. 
Rachel Ee, P.L. 
Keywords: Breast cancer resistance protein
Chalcones
Drug accumulation
Inhibitors
Multidrug resistance
Issue Date: 2-Sep-2008
Citation: Han, Y., Riwanto, M., Go, M.-L., Rachel Ee, P.L. (2008-09-02). Modulation of breast cancer resistance protein (BCRP/ABCG2) by non-basic chalcone analogues. European Journal of Pharmaceutical Sciences 35 (1-2) : 30-41. ScholarBank@NUS Repository. https://doi.org/10.1016/j.ejps.2008.06.001
Abstract: Chalcones are biosynthetic precursors of flavonoids found to possess cytotoxic and chemopreventive activities. In this study, 17 non-basic chalcone analogues were synthesized and evaluated for their ability to modulate the function of either the human wild-type (482R) or mutant (482T) breast cancer resistance protein (BCRP/ABCG2) stably expressed in breast cancer MDA-MB-231 cells. At 5 μM, chalcones with 2,4-dimethoxy groups or 2,4-dihydroxyl groups on ring A were found to increase mitoxantrone accumulation to a greater extent than an established BCRP inhibitor, fumitremorgin C. At the same time, these chalcones had negligible effect on calcein accumulation in P-glycoprotein overexpressing MDCKII cells, indicating their potential as selective BCRP inhibitors. Functionally, these compounds were able to increase the sensitivity of BCRP-overexpressing cancer cells to mitoxantrone by 2-5-fold. The effect of chalcone compounds on both wild-type and mutant BCRP ATPase activity was also examined and variable effects were observed. A stimulatory effect was mostly observed with chalcones with 2,4-dimethoxy substitution on ring A which were earmarked as good BCRP inhibitors in the MX accumulation and cytotoxicity assays. These findings underscore the potential of methoxylated and hydroxylated chalcones as selective and potent inhibitors of BCRP whose mode of action may not involve the inhibition of ATPase activity. © 2008 Elsevier B.V. All rights reserved.
Source Title: European Journal of Pharmaceutical Sciences
URI: http://scholarbank.nus.edu.sg/handle/10635/106158
ISSN: 09280987
DOI: 10.1016/j.ejps.2008.06.001
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