Interaction of plant cannabinoids with the multidrug transporter ABCC1 (MRP1).
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.
Holland
Michelle L
ML
Bosch Institute, The University of Sydney, New South Wales, Australia.
Allen
John D
JD
Arnold
Jonathon C
JC
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000187:drug effects* / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D002185:Cannabidiol / Q000008:administration & dosage / Q000494:pharmacology; D002186:Cannabinoids / Q000008:administration & dosage / Q000494:pharmacology*; D002187:Cannabinol / Q000008:administration & dosage / Q000494:pharmacology; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D013759:Dronabinol / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D015870:Gene Expression; D006801:Humans; D007313:Insecta; D010051:Ovarian Neoplasms / Q000378:metabolism*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002186:Cannabinoids; D010936:Plant Extracts; D002185:Cannabidiol; D013759:Dronabinol; D002187:Cannabinol; D000251:Adenosine Triphosphatases