Abstract
The ATP-binding cassette (ABC) transporter ABCC1, or multidrug resistance-related protein 1 (MRP1) is implicated in Phase II 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 ABCC1. 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>Delta(9)-tetrahydrocannabinol. Cannabinoid inhibition of ABCC1 was confirmed using insect cell membrane MRP1 ATPase assays. These results demonstrate that cannabinoids inhibit ABCC1.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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ATP Binding Cassette Transporter, Subfamily B
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / drug effects*
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
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Adenosine Triphosphatases / metabolism
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Animals
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Biological Transport
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Cannabidiol / administration & dosage
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Cannabidiol / pharmacology
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Cannabinoids / administration & dosage
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Cannabinoids / pharmacology*
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Cannabinol / administration & dosage
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Cannabinol / pharmacology
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Cell Line, Tumor
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Cell Membrane / drug effects
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Cell Membrane / metabolism
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Dronabinol / administration & dosage
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Dronabinol / pharmacology
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Female
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Gene Expression
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Humans
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Insecta
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Ovarian Neoplasms / metabolism*
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Plant Extracts / chemistry
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Plant Extracts / pharmacology*
Substances
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ABCB1 protein, human
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ATP Binding Cassette Transporter, Subfamily B
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ATP Binding Cassette Transporter, Subfamily B, Member 1
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Cannabinoids
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Plant Extracts
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Cannabidiol
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Dronabinol
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Cannabinol
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Adenosine Triphosphatases