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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
PeerJ Inc.
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3775628/ https://www.ncbi.nlm.nih.gov/pubmed/24058883 http://dx.doi.org/10.7717/peerj.153 |
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author | Feinshtein, Valeria Erez, Offer Ben-Zvi, Zvi Erez, Noam Eshkoli, Tamar Sheizaf, Boaz Sheiner, Eyal Huleihel, Mahmud Holcberg, Gershon |
author_facet | Feinshtein, Valeria Erez, Offer Ben-Zvi, Zvi Erez, Noam Eshkoli, Tamar Sheizaf, Boaz Sheiner, Eyal Huleihel, Mahmud Holcberg, Gershon |
author_sort | Feinshtein, Valeria |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-3775628 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | PeerJ Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-37756282013-09-20 Cannabidiol changes P-gp and BCRP expression in trophoblast cell lines Feinshtein, Valeria Erez, Offer Ben-Zvi, Zvi Erez, Noam Eshkoli, Tamar Sheizaf, Boaz Sheiner, Eyal Huleihel, Mahmud Holcberg, Gershon PeerJ Gynecology and Obstetrics 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. PeerJ Inc. 2013-09-12 /pmc/articles/PMC3775628/ /pubmed/24058883 http://dx.doi.org/10.7717/peerj.153 Text en © 2013 Feinshtein et al. http://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Gynecology and Obstetrics Feinshtein, Valeria Erez, Offer Ben-Zvi, Zvi Erez, Noam Eshkoli, Tamar Sheizaf, Boaz Sheiner, Eyal Huleihel, Mahmud Holcberg, Gershon Cannabidiol changes P-gp and BCRP expression in trophoblast cell lines |
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 | Gynecology and Obstetrics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3775628/ https://www.ncbi.nlm.nih.gov/pubmed/24058883 http://dx.doi.org/10.7717/peerj.153 |
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