Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Feinshtein, Valeria, Erez, Offer, Ben-Zvi, Zvi, Erez, Noam, Eshkoli, Tamar, Sheizaf, Boaz, Sheiner, Eyal, Huleihel, Mahmud, Holcberg, Gershon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: PeerJ Inc. 2013
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
_version_ 1782477399914446848
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
work_keys_str_mv AT feinshteinvaleria cannabidiolchangespgpandbcrpexpressionintrophoblastcelllines
AT erezoffer cannabidiolchangespgpandbcrpexpressionintrophoblastcelllines
AT benzvizvi cannabidiolchangespgpandbcrpexpressionintrophoblastcelllines
AT ereznoam cannabidiolchangespgpandbcrpexpressionintrophoblastcelllines
AT eshkolitamar cannabidiolchangespgpandbcrpexpressionintrophoblastcelllines
AT sheizafboaz cannabidiolchangespgpandbcrpexpressionintrophoblastcelllines
AT sheinereyal cannabidiolchangespgpandbcrpexpressionintrophoblastcelllines
AT huleihelmahmud cannabidiolchangespgpandbcrpexpressionintrophoblastcelllines
AT holcberggershon cannabidiolchangespgpandbcrpexpressionintrophoblastcelllines