[{"id":137,"uid":"NPDI-1wiJBw","name":"Cannabidiol changes P-gp and BCRP expression in trophoblast cell lines.","napdiIdentifier":null,"overallSummary":"
Objectives.Marijuana is the most commonly used illicit drug during pregnancy. Due
\r\nto high lipophilicity, cannabinoids can easily penetrate physiological barriers like
\r\nthe human placenta and jeopardize the developing fetus.We evaluated the impact
\r\nof cannabidiol (CBD), a major non-psychoactive cannabinoid, on P-glycoprotein
\r\n(P-gp) and Breast Cancer Resistance Protein (BCRP) expression, and P-gp function
\r\nin a placental model, BeWo and Jar choriocarcinoma cell lines (using P-gp induced
\r\nMCF7 cells (MCF7/P-gp) for comparison).
\r\nStudy design. Following the establishment of the basal expression of these transporters
\r\nin the membrane fraction of all three cell lines, P-gp and BCRP protein
\r\nand mRNA levels were determined following chronic (24–72 h) exposure to CBD,
\r\nby Western Blot and qPCR. CBD impact on P-gp efflux function was examined
\r\nby uptake of specific P-gp fluorescent substrates (calcein-AM, DiOC2(3) and rhodamine123(
\r\nrh123)). Cyclosporine A (CsA) served as a positive control.
\r\nResults. Chronic exposure to CBD resulted in significant changes in the protein and
\r\nmRNA levels of both transporters. While P-gp was down-regulated, BCRP levels
\r\nwere up-regulated in the choriocarcinoma cell lines. CBD had a remarkably different
\r\ninfluence on P-gp and BCRP expression in MCF7/P-gp cells, demonstrating that
\r\nthese are cell type specific effects. P-gp dependent efflux (of calcein, DiOC2(3) and
\r\nrh123) was inhibited upon short-termexposure to CBD.
\r\nConclusions. Our study shows that CBD might alter P-gp and BCRP expression in
\r\nthe human placenta, and inhibit P-gp efflux function.We conclude that marijuana
\r\nuse during pregnancy may reduce placental protective functions and change its
\r\nmorphological and physiological characteristics.
","pubmedId":24058883,"embaseId":null,"croIdentifier":"Department of Clinical Biochemistry and Pharmacology, Ben-Gurion University of the Negev , Israel","croInformation":"Department of Clinical Biochemistry and Pharmacology, Ben-Gurion University of the Negev , Israel","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":733,"uid":"NPDI-2LIXDQ","name":"Down regulation of P-gp transporter (protein) by Cannabidiol","overallEffect":-1,"isControlData":false,"isIc50Shift":false,"croCutoff":"N/A
","croIdentifier":null,"comment":null,"experimentalConditionsComment":null,"resultsComment":"figure 3","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":115,"cytochromeB5Id":null,"studyId":137,"experimentTypeId":6,"testSystemId":41,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType":{"id":6,"name":"In Vitro Transporter Induction","isInVitro":true,"isTransporter":true,"isEnzyme":false,"purl":"http://purl.obolibrary.org/obo/DIDEO_00005002"},"objectCompound":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":11,"name":"P-gp (ABCB1)","conceptId":null,"experiment_transporter_xref":{"experiment":733,"transporte":11}}],"quantifiedMetabolites":[]},{"id":727,"uid":"NPDI-spUvqw","name":"Induction of BCRP transporter (mRNA) by Cannabidiol","overallEffect":1,"isControlData":false,"isIc50Shift":false,"croCutoff":"N/A
","croIdentifier":null,"comment":null,"experimentalConditionsComment":null,"resultsComment":"figure 5","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":115,"cytochromeB5Id":null,"studyId":137,"experimentTypeId":6,"testSystemId":41,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType":{"id":6,"name":"In Vitro Transporter Induction","isInVitro":true,"isTransporter":true,"isEnzyme":false,"purl":"http://purl.obolibrary.org/obo/DIDEO_00005002"},"objectCompound":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":1,"name":"BCRP (ABCG2)","conceptId":null,"experiment_transporter_xref":{"experiment":727,"transporte":1}}],"quantifiedMetabolites":[]},{"id":729,"uid":"NPDI-mbNW9A","name":"Induction of P-gp transporter (protein) by Cannabidiol","overallEffect":1,"isControlData":false,"isIc50Shift":false,"croCutoff":"N/A
","croIdentifier":null,"comment":null,"experimentalConditionsComment":null,"resultsComment":"figure 4","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":115,"cytochromeB5Id":null,"studyId":137,"experimentTypeId":6,"testSystemId":42,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType":{"id":6,"name":"In Vitro Transporter Induction","isInVitro":true,"isTransporter":true,"isEnzyme":false,"purl":"http://purl.obolibrary.org/obo/DIDEO_00005002"},"objectCompound":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":11,"name":"P-gp (ABCB1)","conceptId":null,"experiment_transporter_xref":{"experiment":729,"transporte":11}}],"quantifiedMetabolites":[]},{"id":730,"uid":"NPDI-PaO28A","name":"Non-induction of BCRP transporter (protein) by Cannabiodiol","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":"N/A
","croIdentifier":null,"comment":null,"experimentalConditionsComment":null,"resultsComment":"figure 4","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":115,"cytochromeB5Id":null,"studyId":137,"experimentTypeId":6,"testSystemId":42,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType":{"id":6,"name":"In Vitro Transporter Induction","isInVitro":true,"isTransporter":true,"isEnzyme":false,"purl":"http://purl.obolibrary.org/obo/DIDEO_00005002"},"objectCompound":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":1,"name":"BCRP (ABCG2)","conceptId":null,"experiment_transporter_xref":{"experiment":730,"transporte":1}}],"quantifiedMetabolites":[]},{"id":737,"uid":"NPDI-Aasqdw","name":"Induction of BCRP transporter (protein) by Cannabidiol","overallEffect":1,"isControlData":false,"isIc50Shift":false,"croCutoff":"N/A
","croIdentifier":null,"comment":null,"experimentalConditionsComment":null,"resultsComment":"FIGURE 2","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":115,"cytochromeB5Id":null,"studyId":137,"experimentTypeId":6,"testSystemId":40,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType":{"id":6,"name":"In Vitro Transporter Induction","isInVitro":true,"isTransporter":true,"isEnzyme":false,"purl":"http://purl.obolibrary.org/obo/DIDEO_00005002"},"objectCompound":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":1,"name":"BCRP (ABCG2)","conceptId":null,"experiment_transporter_xref":{"experiment":737,"transporte":1}}],"quantifiedMetabolites":[]},{"id":728,"uid":"NPDI-E7xthw","name":"Down regulation of P-gp (mRNA) by Cannabidiol","overallEffect":-1,"isControlData":false,"isIc50Shift":false,"croCutoff":"N/A
","croIdentifier":null,"comment":null,"experimentalConditionsComment":null,"resultsComment":"figure 5","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":115,"cytochromeB5Id":null,"studyId":137,"experimentTypeId":6,"testSystemId":41,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType":{"id":6,"name":"In Vitro Transporter Induction","isInVitro":true,"isTransporter":true,"isEnzyme":false,"purl":"http://purl.obolibrary.org/obo/DIDEO_00005002"},"objectCompound":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":11,"name":"P-gp (ABCB1)","conceptId":null,"experiment_transporter_xref":{"experiment":728,"transporte":11}}],"quantifiedMetabolites":[]},{"id":725,"uid":"NPDI-jHdxpA","name":"Induction (mRNA) of BCRP transporter with Cannabidiol","overallEffect":1,"isControlData":false,"isIc50Shift":false,"croCutoff":"N/A
","croIdentifier":null,"comment":null,"experimentalConditionsComment":null,"resultsComment":"figure 5","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":115,"cytochromeB5Id":null,"studyId":137,"experimentTypeId":6,"testSystemId":40,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType":{"id":6,"name":"In Vitro Transporter Induction","isInVitro":true,"isTransporter":true,"isEnzyme":false,"purl":"http://purl.obolibrary.org/obo/DIDEO_00005002"},"objectCompound":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":1,"name":"BCRP (ABCG2)","conceptId":null,"experiment_transporter_xref":{"experiment":725,"transporte":1}}],"quantifiedMetabolites":[]},{"id":732,"uid":"NPDI-Ix-KKg","name":"Induction of BCRP transporter (protein) by Cannabidiol","overallEffect":1,"isControlData":false,"isIc50Shift":false,"croCutoff":"N/A
","croIdentifier":null,"comment":null,"experimentalConditionsComment":null,"resultsComment":"FIGURE 3","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":115,"cytochromeB5Id":null,"studyId":137,"experimentTypeId":6,"testSystemId":41,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType":{"id":6,"name":"In Vitro Transporter Induction","isInVitro":true,"isTransporter":true,"isEnzyme":false,"purl":"http://purl.obolibrary.org/obo/DIDEO_00005002"},"objectCompound":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":1,"name":"BCRP (ABCG2)","conceptId":null,"experiment_transporter_xref":{"experiment":732,"transporte":1}}],"quantifiedMetabolites":[]},{"id":669,"uid":"NPDI-IoxesQ","name":"Inhibition of P-gp by Cannabidiol 10 µM","overallEffect":1,"isControlData":false,"isIc50Shift":false,"croCutoff":"N/A
","croIdentifier":null,"comment":null,"experimentalConditionsComment":null,"resultsComment":"N/A
","croIdentifier":null,"comment":null,"experimentalConditionsComment":null,"resultsComment":"N/A
","croIdentifier":null,"comment":null,"experimentalConditionsComment":null,"resultsComment":null,"internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":115,"cytochromeB5Id":null,"studyId":137,"experimentTypeId":6,"testSystemId":40,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType":{"id":6,"name":"In Vitro Transporter Induction","isInVitro":true,"isTransporter":true,"isEnzyme":false,"purl":"http://purl.obolibrary.org/obo/DIDEO_00005002"},"objectCompound":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":11,"name":"P-gp (ABCB1)","conceptId":null,"experiment_transporter_xref":{"experiment":735,"transporte":11}}],"quantifiedMetabolites":[]},{"id":734,"uid":"NPDI-29ER6A","name":"Down regulation of P-gp transporter (protein) by Cannabidiol","overallEffect":-1,"isControlData":false,"isIc50Shift":false,"croCutoff":"N/A
","croIdentifier":null,"comment":null,"experimentalConditionsComment":null,"resultsComment":"figure 2","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":115,"cytochromeB5Id":null,"studyId":137,"experimentTypeId":6,"testSystemId":40,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType":{"id":6,"name":"In Vitro Transporter Induction","isInVitro":true,"isTransporter":true,"isEnzyme":false,"purl":"http://purl.obolibrary.org/obo/DIDEO_00005002"},"objectCompound":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":11,"name":"P-gp (ABCB1)","conceptId":null,"experiment_transporter_xref":{"experiment":734,"transporte":11}}],"quantifiedMetabolites":[]},{"id":671,"uid":"NPDI-cqaAMA","name":"Inhibition of P-gp by Cannabidiol 10µM","overallEffect":1,"isControlData":false,"isIc50Shift":false,"croCutoff":"N/A
","croIdentifier":null,"comment":null,"experimentalConditionsComment":null,"resultsComment":"N/A
","croIdentifier":null,"comment":null,"experimentalConditionsComment":null,"resultsComment":"N/A
","croIdentifier":null,"comment":null,"experimentalConditionsComment":null,"resultsComment":"figure 3","internalComment":null,"objectCompoundId":null,"objectMetaboliteCompoundId":null,"precipitantCompoundId":115,"cytochromeB5Id":null,"studyId":137,"experimentTypeId":6,"testSystemId":41,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType":{"id":6,"name":"In Vitro Transporter Induction","isInVitro":true,"isTransporter":true,"isEnzyme":false,"purl":"http://purl.obolibrary.org/obo/DIDEO_00005002"},"objectCompound":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":1,"name":"BCRP (ABCG2)","conceptId":null,"experiment_transporter_xref":{"experiment":731,"transporte":1}}],"quantifiedMetabolites":[]}]}]