[{"id":139,"uid":"NPDI-ahQtSQ","name":"Interaction of plant cannabinoids with the multidrug transporter ABCC1 (MRP1)","napdiIdentifier":null,"overallSummary":"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&gt;cannabinol&gt;Delta(9)-tetrahydrocannabinol. Cannabinoid inhibition of ABCC1 was confirmed using insect cell membrane MRP1 ATPase assays. These results demonstrate that cannabinoids inhibit ABCC1.","pubmedId":18619955,"embaseId":null,"croIdentifier":"School of Medical Sciences (Pharmacology) and Bosch Institute, The University of Sydney, New South Wales, Australia","croInformation":"School of Medical Sciences (Pharmacology) and Bosch Institute, The University of Sydney, New South Wales, Australia","dateStart":null,"dateEnd":null,"internalComment":"A published report from the literature. Data entered by CB and review by RB.","status":"published","compoundId":null,"naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","naturalProductSampleId":null,"studySourceTypeId":1,"naturalProduct":{"uid":"NP-0162af79-839e-40e2-af47-361c659061e9","binomial":"Cannabis sativa","name":"Cannabis","itis":null,"srs":"4495dd37-943e-434d-bf30-ea9172d543c8","source_id":"","conceptId":null},"compound":null,"studySourceType":{"id":1,"name":"Published report"},"experiments":[{"id":674,"uid":"NPDI-qeGJYg","name":"Negligible inhibition of ABCC1 by Cannabidiol","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":"<p>Not provided. A common convention is that IC50 &gt; 100 micM signals negligible inhibition</p>","croIdentifier":null,"comment":null,"experimentalConditionsComment":"<p>incubation time with two phases, cells and natural products for 30 min and then with Fluo3 for another 60 min.</p>","resultsComment":"<div><span lang=\"EN-US\">“Measurements show 50% reduction in transport using increase in intracellular accumulation based on % of parent concentration”</span></div>","internalComment":"<p style=\"margin: 0px; font-stretch: normal; font-size: 8px; line-height: normal; font-family: Times;\">Cell line = human ABCC1 transduced subline (2008/MRP1)</p>","objectCompoundId":216,"objectMetaboliteCompoundId":null,"precipitantCompoundId":115,"cytochromeB5Id":null,"studyId":139,"experimentTypeId":5,"testSystemId":39,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType":{"id":5,"name":"In Vitro Transporter Inhibition","isInVitro":true,"isTransporter":true,"isEnzyme":false,"purl":"http://purl.obolibrary.org/obo/DIDEO_00000060"},"objectCompound":{"id":216,"name":"fluo3","unii":null,"inChIKey":"OZLGRUXZXMRXGP-UHFFFAOYSA-N","publicDescription":null,"internalComment":null,"conceptId":null,"enantiomerOfId":null},"precipitantCompound":{"id":115,"name":"cannabidiol","unii":null,"inChIKey":"QHMBSVQNZZTUGM-ZWKOTPCHSA-N","publicDescription":null,"internalComment":null,"conceptId":null,"enantiomerOfId":null},"objectMetaboliteCompound":null,"enzymes":[],"transporters":[{"id":15,"name":"ABCC1","conceptId":null,"experiment_transporter_xref":{"experiment":674,"transporte":15}}],"quantifiedMetabolites":[]},{"id":679,"uid":"NPDI-7RWWrg","name":"Inhibition of ABCC1 by Cannabinol","overallEffect":1,"isControlData":false,"isIc50Shift":false,"croCutoff":"<p>NA</p>","croIdentifier":null,"comment":null,"experimentalConditionsComment":"<div><span lang=\"EN-US\">incubation time with two phases, cells and natural products for 30 min and then with Vincristine for another 90 min.</span></div>","resultsComment":"<div><span lang=\"EN-US\">Measurements show 50% reduction in transport using increase in intracellular accumulation based on % of parent concentration.</span></div>","internalComment":null,"objectCompoundId":219,"objectMetaboliteCompoundId":null,"precipitantCompoundId":153,"cytochromeB5Id":null,"studyId":139,"experimentTypeId":5,"testSystemId":38,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType":{"id":5,"name":"In Vitro Transporter Inhibition","isInVitro":true,"isTransporter":true,"isEnzyme":false,"purl":"http://purl.obolibrary.org/obo/DIDEO_00000060"},"objectCompound":{"id":219,"name":"vincristine","unii":null,"inChIKey":"OGWKCGZFUXNPDA-XQKSVPLYSA-N","publicDescription":null,"internalComment":null,"conceptId":null,"enantiomerOfId":null},"precipitantCompound":{"id":153,"name":"cannabinol","unii":null,"inChIKey":"VBGLYOIFKLUMQG-UHFFFAOYSA-N","publicDescription":null,"internalComment":null,"conceptId":null,"enantiomerOfId":null},"objectMetaboliteCompound":null,"enzymes":[],"transporters":[{"id":15,"name":"ABCC1","conceptId":null,"experiment_transporter_xref":{"experiment":679,"transporte":15}}],"quantifiedMetabolites":[]},{"id":675,"uid":"NPDI-JnMHww","name":"Negligible inhibition of ABCC1 by Cannabinol","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":"<p>Not provided. A common convention is that IC50 &gt; 100 micM signals negligible inhibition</p>","croIdentifier":null,"comment":null,"experimentalConditionsComment":"<div><span lang=\"EN-US\">“incubation time with two phases, cells and natural products for 30 min and then with Fluo3 for another 60 min”</span></div>","resultsComment":"<div><span lang=\"EN-US\">“Measurements show 50% reduction in transport using increase in intracellular accumulation based on % of parent concentration”</span></div>","internalComment":null,"objectCompoundId":216,"objectMetaboliteCompoundId":null,"precipitantCompoundId":153,"cytochromeB5Id":null,"studyId":139,"experimentTypeId":5,"testSystemId":39,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType":{"id":5,"name":"In Vitro Transporter Inhibition","isInVitro":true,"isTransporter":true,"isEnzyme":false,"purl":"http://purl.obolibrary.org/obo/DIDEO_00000060"},"objectCompound":{"id":216,"name":"fluo3","unii":null,"inChIKey":"OZLGRUXZXMRXGP-UHFFFAOYSA-N","publicDescription":null,"internalComment":null,"conceptId":null,"enantiomerOfId":null},"precipitantCompound":{"id":153,"name":"cannabinol","unii":null,"inChIKey":"VBGLYOIFKLUMQG-UHFFFAOYSA-N","publicDescription":null,"internalComment":null,"conceptId":null,"enantiomerOfId":null},"objectMetaboliteCompound":null,"enzymes":[],"transporters":[{"id":15,"name":"ABCC1","conceptId":null,"experiment_transporter_xref":{"experiment":675,"transporte":15}}],"quantifiedMetabolites":[]},{"id":676,"uid":"NPDI-PWUeog","name":"Inhibition of ABCC1 by Cannabidiol","overallEffect":1,"isControlData":false,"isIc50Shift":false,"croCutoff":"<p>NA</p>","croIdentifier":null,"comment":null,"experimentalConditionsComment":"<div><span lang=\"EN-US\">incubation time with two phases, cells and natural products for 30 min and then with Vincristine for another 90 min</span></div>","resultsComment":"<div><span lang=\"EN-US\">Measurements show 50% reduction in transport using increase in intracellular accumulation based on % of parent concentration.</span></div>","internalComment":null,"objectCompoundId":219,"objectMetaboliteCompoundId":null,"precipitantCompoundId":115,"cytochromeB5Id":null,"studyId":139,"experimentTypeId":5,"testSystemId":38,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType":{"id":5,"name":"In Vitro Transporter Inhibition","isInVitro":true,"isTransporter":true,"isEnzyme":false,"purl":"http://purl.obolibrary.org/obo/DIDEO_00000060"},"objectCompound":{"id":219,"name":"vincristine","unii":null,"inChIKey":"OGWKCGZFUXNPDA-XQKSVPLYSA-N","publicDescription":null,"internalComment":null,"conceptId":null,"enantiomerOfId":null},"precipitantCompound":{"id":115,"name":"cannabidiol","unii":null,"inChIKey":"QHMBSVQNZZTUGM-ZWKOTPCHSA-N","publicDescription":null,"internalComment":null,"conceptId":null,"enantiomerOfId":null},"objectMetaboliteCompound":null,"enzymes":[],"transporters":[{"id":15,"name":"ABCC1","conceptId":null,"experiment_transporter_xref":{"experiment":676,"transporte":15}}],"quantifiedMetabolites":[]},{"id":678,"uid":"NPDI-uUyadQ","name":"Negligible inhibition of ABCC1 by THC","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":"<p>Not provided. A common convention is that IC50 &gt; 100 micM signals negligible inhibition</p>","croIdentifier":null,"comment":null,"experimentalConditionsComment":"<div><span lang=\"EN-US\">incubation time with two phases, cells and natural products for 30 min and then with Vincristine for another 90 min</span></div>","resultsComment":"<div><span lang=\"EN-US\">Measurements show 50% reduction in transport using increase in intracellular accumulation based on % of parent concentration.</span></div>","internalComment":null,"objectCompoundId":219,"objectMetaboliteCompoundId":null,"precipitantCompoundId":118,"cytochromeB5Id":null,"studyId":139,"experimentTypeId":5,"testSystemId":38,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType":{"id":5,"name":"In Vitro Transporter Inhibition","isInVitro":true,"isTransporter":true,"isEnzyme":false,"purl":"http://purl.obolibrary.org/obo/DIDEO_00000060"},"objectCompound":{"id":219,"name":"vincristine","unii":null,"inChIKey":"OGWKCGZFUXNPDA-XQKSVPLYSA-N","publicDescription":null,"internalComment":null,"conceptId":null,"enantiomerOfId":null},"precipitantCompound":{"id":118,"name":"delta-9-tetrahydrocannabinol","unii":null,"inChIKey":"CYQFCXCEBYINGO-UHFFFAOYSA-N","publicDescription":null,"internalComment":null,"conceptId":null,"enantiomerOfId":null},"objectMetaboliteCompound":null,"enzymes":[],"transporters":[{"id":15,"name":"ABCC1","conceptId":null,"experiment_transporter_xref":{"experiment":678,"transporte":15}}],"quantifiedMetabolites":[]},{"id":677,"uid":"NPDI-lNsNoQ","name":"Negligible inhibition of ABCC1 by THC","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":"<p>Not provided. A common convention is that IC50 &gt; 100 micM signals negligible inhibition</p>","croIdentifier":null,"comment":null,"experimentalConditionsComment":"<div><span lang=\"EN-US\">“incubation time with two phases, cells and natural products for 30 min and then with Fluo3 for another 60 min”</span></div>","resultsComment":"<div><span lang=\"EN-US\">“Measurements show 50% reduction in transport using increase in intracellular accumulation based on % of parent concentration”</span></div>","internalComment":null,"objectCompoundId":216,"objectMetaboliteCompoundId":null,"precipitantCompoundId":118,"cytochromeB5Id":null,"studyId":139,"experimentTypeId":5,"testSystemId":39,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType":{"id":5,"name":"In Vitro Transporter Inhibition","isInVitro":true,"isTransporter":true,"isEnzyme":false,"purl":"http://purl.obolibrary.org/obo/DIDEO_00000060"},"objectCompound":{"id":216,"name":"fluo3","unii":null,"inChIKey":"OZLGRUXZXMRXGP-UHFFFAOYSA-N","publicDescription":null,"internalComment":null,"conceptId":null,"enantiomerOfId":null},"precipitantCompound":{"id":118,"name":"delta-9-tetrahydrocannabinol","unii":null,"inChIKey":"CYQFCXCEBYINGO-UHFFFAOYSA-N","publicDescription":null,"internalComment":null,"conceptId":null,"enantiomerOfId":null},"objectMetaboliteCompound":null,"enzymes":[],"transporters":[{"id":15,"name":"ABCC1","conceptId":null,"experiment_transporter_xref":{"experiment":677,"transporte":15}}],"quantifiedMetabolites":[]}]}]