Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 591, Issue 1-3, Pages 128-131Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejphar.2008.06.079
Keywords
ABC transporter; multidrug resistance-related protein 1; ABCC1; cannabinoid
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Funding
- Australian Postgraduate Award
- Cancer Institute NSW Research Scholar Award
- Cancer Institute NSW Fellowship
- NHMRC [226905]
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The ATP-binding cassette (ABC) transporter ABCC1, or multidrug resistance-related protein 1 (MRP1) is implicated in Phase 11 metabolism and multidrug resistance as it effluxes substrate anticancer drugs. As cannabinoids inhibit two related ABC transporters, P-glycoprotein and ABCG2, here we examined whether they also inhibit ABCCl. Indeed, the cannabinoids enhanced the intracellular accumulation of two ABCC1 substrates, Fluo3 and vincristine, in ovarian carcinoma cells over-expressing ABCC1 (2008/MRP1) with a rank order of potency: cannabidiol>cannabinol>Ag-tetrahydrocannabinol. Cannabinoid inhibition of ABCC1 was confirmed using insect cell membrane MRP1 ATPase assays. These results demonstrate that cannabinoids inhibit ABCC1. Crown Copyright (C) 2008 Published by Elsevier B.V. All rights reserved.
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