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Toxicity of anticancer drugs in human placental tissue explants and trophoblast cell lines
The application of anticancer drugs during pregnancy is associated with placenta-related adverse pregnancy outcomes. Therefore, it is important to study placental toxicity of anticancer drugs. The aim of this study was to compare effects on viability and steroidogenesis in placental tissue explants...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870638/ https://www.ncbi.nlm.nih.gov/pubmed/33083868 http://dx.doi.org/10.1007/s00204-020-02925-w |
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author | Eliesen, Gaby A. M. van Hove, Hedwig Meijer, Maartje H. van den Broek, Petra H. H. Pertijs, Jeanne Roeleveld, Nel van Drongelen, Joris Russel, Frans G. M. Greupink, Rick |
author_facet | Eliesen, Gaby A. M. van Hove, Hedwig Meijer, Maartje H. van den Broek, Petra H. H. Pertijs, Jeanne Roeleveld, Nel van Drongelen, Joris Russel, Frans G. M. Greupink, Rick |
author_sort | Eliesen, Gaby A. M. |
collection | PubMed |
description | The application of anticancer drugs during pregnancy is associated with placenta-related adverse pregnancy outcomes. Therefore, it is important to study placental toxicity of anticancer drugs. The aim of this study was to compare effects on viability and steroidogenesis in placental tissue explants and trophoblast cell lines. Third trimester placental tissue explants were exposed for 72 h (culture day 4–7) to a concentration range of doxorubicin, paclitaxel, cisplatin, carboplatin, crizotinib, gefitinib, imatinib, or sunitinib. JEG-3, undifferentiated BeWo, and syncytialised BeWo cells were exposed for 48 h to the same drugs and concentrations. After exposure, tissue and cell viability were assessed and progesterone and estrone levels were quantified in culture medium. Apart from paclitaxel, all compounds affected both cell and tissue viability at clinically relevant concentrations. Paclitaxel affected explant viability moderately, while it reduced cell viability by 50% or more in all cell lines, at 3–10 nM. Doxorubicin (1 µM) reduced viability in explants to 83 ± 7% of control values, whereas it fully inhibited viability in all cell types. Interference with steroid release in explants was difficult to study due to large variability in measurements, but syncytialised BeWo cells proved suitable for this purpose. We found that 1 µM sunitinib reduced progesterone release to 76 ± 6% of control values, without affecting cell viability. While we observed differences between the models for paclitaxel and doxorubicin, most anticancer drugs affected viability significantly in both placental explants and trophoblast cell lines. Taken together, the placenta should be recognized as a potential target organ for toxicity of anticancer drugs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00204-020-02925-w) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-7870638 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-78706382021-02-16 Toxicity of anticancer drugs in human placental tissue explants and trophoblast cell lines Eliesen, Gaby A. M. van Hove, Hedwig Meijer, Maartje H. van den Broek, Petra H. H. Pertijs, Jeanne Roeleveld, Nel van Drongelen, Joris Russel, Frans G. M. Greupink, Rick Arch Toxicol In Vitro Systems The application of anticancer drugs during pregnancy is associated with placenta-related adverse pregnancy outcomes. Therefore, it is important to study placental toxicity of anticancer drugs. The aim of this study was to compare effects on viability and steroidogenesis in placental tissue explants and trophoblast cell lines. Third trimester placental tissue explants were exposed for 72 h (culture day 4–7) to a concentration range of doxorubicin, paclitaxel, cisplatin, carboplatin, crizotinib, gefitinib, imatinib, or sunitinib. JEG-3, undifferentiated BeWo, and syncytialised BeWo cells were exposed for 48 h to the same drugs and concentrations. After exposure, tissue and cell viability were assessed and progesterone and estrone levels were quantified in culture medium. Apart from paclitaxel, all compounds affected both cell and tissue viability at clinically relevant concentrations. Paclitaxel affected explant viability moderately, while it reduced cell viability by 50% or more in all cell lines, at 3–10 nM. Doxorubicin (1 µM) reduced viability in explants to 83 ± 7% of control values, whereas it fully inhibited viability in all cell types. Interference with steroid release in explants was difficult to study due to large variability in measurements, but syncytialised BeWo cells proved suitable for this purpose. We found that 1 µM sunitinib reduced progesterone release to 76 ± 6% of control values, without affecting cell viability. While we observed differences between the models for paclitaxel and doxorubicin, most anticancer drugs affected viability significantly in both placental explants and trophoblast cell lines. Taken together, the placenta should be recognized as a potential target organ for toxicity of anticancer drugs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00204-020-02925-w) contains supplementary material, which is available to authorized users. Springer Berlin Heidelberg 2020-10-20 2021 /pmc/articles/PMC7870638/ /pubmed/33083868 http://dx.doi.org/10.1007/s00204-020-02925-w Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | In Vitro Systems Eliesen, Gaby A. M. van Hove, Hedwig Meijer, Maartje H. van den Broek, Petra H. H. Pertijs, Jeanne Roeleveld, Nel van Drongelen, Joris Russel, Frans G. M. Greupink, Rick Toxicity of anticancer drugs in human placental tissue explants and trophoblast cell lines |
title | Toxicity of anticancer drugs in human placental tissue explants and trophoblast cell lines |
title_full | Toxicity of anticancer drugs in human placental tissue explants and trophoblast cell lines |
title_fullStr | Toxicity of anticancer drugs in human placental tissue explants and trophoblast cell lines |
title_full_unstemmed | Toxicity of anticancer drugs in human placental tissue explants and trophoblast cell lines |
title_short | Toxicity of anticancer drugs in human placental tissue explants and trophoblast cell lines |
title_sort | toxicity of anticancer drugs in human placental tissue explants and trophoblast cell lines |
topic | In Vitro Systems |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870638/ https://www.ncbi.nlm.nih.gov/pubmed/33083868 http://dx.doi.org/10.1007/s00204-020-02925-w |
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