Cannabidiol changes P-gp and BCRP expression in trophoblast cell lines
Objectives. Marijuana is the most commonly used illicit drug during pregnancy. Due to high lipophilicity, cannabinoids can easily penetrate physiological barriers like the human placenta and jeopardize the developing fetus. We evaluated the impact of cannabidiol (CBD), a major non-psychoactive canna...
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| Format: | Article |
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PeerJ Inc.
2013-09-01
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| Online Access: | https://peerj.com/articles/153.pdf |
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| author | Valeria Feinshtein Offer Erez Zvi Ben-Zvi Noam Erez Tamar Eshkoli Boaz Sheizaf Eyal Sheiner Mahmud Huleihel Gershon Holcberg |
| author_facet | Valeria Feinshtein Offer Erez Zvi Ben-Zvi Noam Erez Tamar Eshkoli Boaz Sheizaf Eyal Sheiner Mahmud Huleihel Gershon Holcberg |
| author_sort | Valeria Feinshtein |
| collection | DOAJ |
| description | Objectives. Marijuana is the most commonly used illicit drug during pregnancy. Due to high lipophilicity, cannabinoids can easily penetrate physiological barriers like the human placenta and jeopardize the developing fetus. We evaluated the impact of cannabidiol (CBD), a major non-psychoactive cannabinoid, on P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP) expression, and P-gp function in a placental model, BeWo and Jar choriocarcinoma cell lines (using P-gp induced MCF7 cells (MCF7/P-gp) for comparison). Study design. Following the establishment of the basal expression of these transporters in the membrane fraction of all three cell lines, P-gp and BCRP protein and mRNA levels were determined following chronic (24–72 h) exposure to CBD, by Western Blot and qPCR. CBD impact on P-gp efflux function was examined by uptake of specific P-gp fluorescent substrates (calcein-AM, DiOC2(3) and rhodamine123(rh123)). Cyclosporine A (CsA) served as a positive control. Results. Chronic exposure to CBD resulted in significant changes in the protein and mRNA levels of both transporters. While P-gp was down-regulated, BCRP levels were up-regulated in the choriocarcinoma cell lines. CBD had a remarkably different influence on P-gp and BCRP expression in MCF7/P-gp cells, demonstrating that these are cell type specific effects. P-gp dependent efflux (of calcein, DiOC2(3) and rh123) was inhibited upon short-term exposure to CBD. Conclusions. Our study shows that CBD might alter P-gp and BCRP expression in the human placenta, and inhibit P-gp efflux function. We conclude that marijuana use during pregnancy may reduce placental protective functions and change its morphological and physiological characteristics. |
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| id | doaj.art-e931fca4d75942bb92dbd619458077a1 |
| institution | Directory Open Access Journal |
| issn | 2167-8359 |
| language | English |
| last_indexed | 2024-03-09T04:31:19Z |
| publishDate | 2013-09-01 |
| publisher | PeerJ Inc. |
| record_format | Article |
| series | PeerJ |
| spelling | doaj.art-e931fca4d75942bb92dbd619458077a12023-12-03T13:36:16ZengPeerJ Inc.PeerJ2167-83592013-09-011e15310.7717/peerj.153153Cannabidiol changes P-gp and BCRP expression in trophoblast cell linesValeria Feinshtein0Offer Erez1Zvi Ben-Zvi2Noam Erez3Tamar Eshkoli4Boaz Sheizaf5Eyal Sheiner6Mahmud Huleihel7Gershon Holcberg8Department of Clinical Biochemistry and Pharmacology, Ben-Gurion University of the Negev, IsraelDepartment of Obstetrics and Gynecology, Soroka University Medical Center, School of Medicine, Faculty of Health Sciences, Ben-Gurion University of the Negev, IsraelDepartment of Clinical Biochemistry and Pharmacology, Ben-Gurion University of the Negev, IsraelDepartment of Clinical Biochemistry and Pharmacology, Ben-Gurion University of the Negev, IsraelDepartment of Obstetrics and Gynecology, Soroka University Medical Center, School of Medicine, Faculty of Health Sciences, Ben-Gurion University of the Negev, IsraelDepartment of Obstetrics and Gynecology, Soroka University Medical Center, School of Medicine, Faculty of Health Sciences, Ben-Gurion University of the Negev, IsraelDepartment of Obstetrics and Gynecology, Soroka University Medical Center, School of Medicine, Faculty of Health Sciences, Ben-Gurion University of the Negev, IsraelThe Shraga Segal Department of Microbiology and Immunology, Ben-Gurion University of the Negev, IsraelDepartment of Obstetrics and Gynecology, Soroka University Medical Center, School of Medicine, Faculty of Health Sciences, Ben-Gurion University of the Negev, IsraelObjectives. Marijuana is the most commonly used illicit drug during pregnancy. Due to high lipophilicity, cannabinoids can easily penetrate physiological barriers like the human placenta and jeopardize the developing fetus. We evaluated the impact of cannabidiol (CBD), a major non-psychoactive cannabinoid, on P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP) expression, and P-gp function in a placental model, BeWo and Jar choriocarcinoma cell lines (using P-gp induced MCF7 cells (MCF7/P-gp) for comparison). Study design. Following the establishment of the basal expression of these transporters in the membrane fraction of all three cell lines, P-gp and BCRP protein and mRNA levels were determined following chronic (24–72 h) exposure to CBD, by Western Blot and qPCR. CBD impact on P-gp efflux function was examined by uptake of specific P-gp fluorescent substrates (calcein-AM, DiOC2(3) and rhodamine123(rh123)). Cyclosporine A (CsA) served as a positive control. Results. Chronic exposure to CBD resulted in significant changes in the protein and mRNA levels of both transporters. While P-gp was down-regulated, BCRP levels were up-regulated in the choriocarcinoma cell lines. CBD had a remarkably different influence on P-gp and BCRP expression in MCF7/P-gp cells, demonstrating that these are cell type specific effects. P-gp dependent efflux (of calcein, DiOC2(3) and rh123) was inhibited upon short-term exposure to CBD. Conclusions. Our study shows that CBD might alter P-gp and BCRP expression in the human placenta, and inhibit P-gp efflux function. We conclude that marijuana use during pregnancy may reduce placental protective functions and change its morphological and physiological characteristics.https://peerj.com/articles/153.pdfCannabidiolMarijuanaBreast Cancer Resistance Protein (BCRP)P-glycoprotein (P-gp)BeWo and Jar cellsHuman placenta |
| spellingShingle | Valeria Feinshtein Offer Erez Zvi Ben-Zvi Noam Erez Tamar Eshkoli Boaz Sheizaf Eyal Sheiner Mahmud Huleihel Gershon Holcberg Cannabidiol changes P-gp and BCRP expression in trophoblast cell lines PeerJ Cannabidiol Marijuana Breast Cancer Resistance Protein (BCRP) P-glycoprotein (P-gp) BeWo and Jar cells Human placenta |
| title | Cannabidiol changes P-gp and BCRP expression in trophoblast cell lines |
| title_full | Cannabidiol changes P-gp and BCRP expression in trophoblast cell lines |
| title_fullStr | Cannabidiol changes P-gp and BCRP expression in trophoblast cell lines |
| title_full_unstemmed | Cannabidiol changes P-gp and BCRP expression in trophoblast cell lines |
| title_short | Cannabidiol changes P-gp and BCRP expression in trophoblast cell lines |
| title_sort | cannabidiol changes p gp and bcrp expression in trophoblast cell lines |
| topic | Cannabidiol Marijuana Breast Cancer Resistance Protein (BCRP) P-glycoprotein (P-gp) BeWo and Jar cells Human placenta |
| url | https://peerj.com/articles/153.pdf |
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