Interaction of plant cannabinoids with the multidrug transporter ABCC1 (MRP1)

✍ Scribed by Michelle L. Holland; John D. Allen; Jonathon C. Arnold

• Book ID: 113587746
• Publisher: Elsevier Science
• Year: 2008
• Tongue: English
• Weight: 217 KB
• Volume: 591
• Category: Article
• ISSN: 0014-2999
• DOI: 10.1016/j.ejphar.2008.06.079

✦ Synopsis

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 N cannabinol N Δ 9 -tetrahydrocannabinol. Cannabinoid inhibition of ABCC1 was confirmed using insect cell membrane MRP1 ATPase assays. These results demonstrate that cannabinoids inhibit ABCC1.