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Induction of metallothionein expression by supplementation of zinc induces resistance against platinum-based treatment in malignant pleural mesothelioma
BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive tumor with a dismal prognosis. Currently, multimodality treatment including chemotherapy with cisplatin or carboplatin in combination with pemetrexed offers the best options. Detoxification of heavy metals in the cell by metallothione...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
AME Publishing Company
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10493783/ https://www.ncbi.nlm.nih.gov/pubmed/37701096 http://dx.doi.org/10.21037/tcr-22-2651 |
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author | Wyrich, Martine Ohlig, Henning Wessolly, Michael Mairinger, Elena Steinborn, Julia Brcic, Luka Hegedus, Balazs Hager, Thomas Greimelmaier, Kristina Wohlschlaeger, Jeremias Mairinger, Fabian D. Borchert, Sabrina |
author_facet | Wyrich, Martine Ohlig, Henning Wessolly, Michael Mairinger, Elena Steinborn, Julia Brcic, Luka Hegedus, Balazs Hager, Thomas Greimelmaier, Kristina Wohlschlaeger, Jeremias Mairinger, Fabian D. Borchert, Sabrina |
author_sort | Wyrich, Martine |
collection | PubMed |
description | BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive tumor with a dismal prognosis. Currently, multimodality treatment including chemotherapy with cisplatin or carboplatin in combination with pemetrexed offers the best options. Detoxification of heavy metals in the cell by metallothioneins (MT) is associated with early failure to platin-based chemotherapy. The induction of MTs gene expression or its enzyme results in saturation by exposure to metal ions such as zinc or cadmium. Its therapeutically effect is still not analyzed in depth. METHODS: In our study, we investigated three MPM cell lines and one fibroblast cell line in the course of cisplatin treatment and supplementation of zinc. Cell state analyses via an enzyme-activity based assay were performed. With this, we were able to analyze apoptosis, necrosis and viability of cells. Additionally, we tested treated cells for changes in metallothionein IIA (MT2A) expression by using quantitative realtime polymerase chain reaction. RESULTS: Zinc supplementation induces gene expression of MT2A. Overall, a zinc dose-dependent induction of apoptosis under platin-based treatment could be observed. This effect could be verified in all analyzed cell lines in varying intensity. CONCLUSIONS: MT expression is induced by zinc in a dose-dependent manner and inhibits a successful cisplatin therapy. Therefore, heavy metal exposure during cisplatin therapy, e.g., via cigarette smoke, might be an important factor. This should be considered in further therapeutic approaches. |
format | Online Article Text |
id | pubmed-10493783 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | AME Publishing Company |
record_format | MEDLINE/PubMed |
spelling | pubmed-104937832023-09-12 Induction of metallothionein expression by supplementation of zinc induces resistance against platinum-based treatment in malignant pleural mesothelioma Wyrich, Martine Ohlig, Henning Wessolly, Michael Mairinger, Elena Steinborn, Julia Brcic, Luka Hegedus, Balazs Hager, Thomas Greimelmaier, Kristina Wohlschlaeger, Jeremias Mairinger, Fabian D. Borchert, Sabrina Transl Cancer Res Original Article BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive tumor with a dismal prognosis. Currently, multimodality treatment including chemotherapy with cisplatin or carboplatin in combination with pemetrexed offers the best options. Detoxification of heavy metals in the cell by metallothioneins (MT) is associated with early failure to platin-based chemotherapy. The induction of MTs gene expression or its enzyme results in saturation by exposure to metal ions such as zinc or cadmium. Its therapeutically effect is still not analyzed in depth. METHODS: In our study, we investigated three MPM cell lines and one fibroblast cell line in the course of cisplatin treatment and supplementation of zinc. Cell state analyses via an enzyme-activity based assay were performed. With this, we were able to analyze apoptosis, necrosis and viability of cells. Additionally, we tested treated cells for changes in metallothionein IIA (MT2A) expression by using quantitative realtime polymerase chain reaction. RESULTS: Zinc supplementation induces gene expression of MT2A. Overall, a zinc dose-dependent induction of apoptosis under platin-based treatment could be observed. This effect could be verified in all analyzed cell lines in varying intensity. CONCLUSIONS: MT expression is induced by zinc in a dose-dependent manner and inhibits a successful cisplatin therapy. Therefore, heavy metal exposure during cisplatin therapy, e.g., via cigarette smoke, might be an important factor. This should be considered in further therapeutic approaches. AME Publishing Company 2023-07-21 2023-08-31 /pmc/articles/PMC10493783/ /pubmed/37701096 http://dx.doi.org/10.21037/tcr-22-2651 Text en 2023 Translational Cancer Research. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | Original Article Wyrich, Martine Ohlig, Henning Wessolly, Michael Mairinger, Elena Steinborn, Julia Brcic, Luka Hegedus, Balazs Hager, Thomas Greimelmaier, Kristina Wohlschlaeger, Jeremias Mairinger, Fabian D. Borchert, Sabrina Induction of metallothionein expression by supplementation of zinc induces resistance against platinum-based treatment in malignant pleural mesothelioma |
title | Induction of metallothionein expression by supplementation of zinc induces resistance against platinum-based treatment in malignant pleural mesothelioma |
title_full | Induction of metallothionein expression by supplementation of zinc induces resistance against platinum-based treatment in malignant pleural mesothelioma |
title_fullStr | Induction of metallothionein expression by supplementation of zinc induces resistance against platinum-based treatment in malignant pleural mesothelioma |
title_full_unstemmed | Induction of metallothionein expression by supplementation of zinc induces resistance against platinum-based treatment in malignant pleural mesothelioma |
title_short | Induction of metallothionein expression by supplementation of zinc induces resistance against platinum-based treatment in malignant pleural mesothelioma |
title_sort | induction of metallothionein expression by supplementation of zinc induces resistance against platinum-based treatment in malignant pleural mesothelioma |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10493783/ https://www.ncbi.nlm.nih.gov/pubmed/37701096 http://dx.doi.org/10.21037/tcr-22-2651 |
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