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Inhibition of Intercellular Cytosolic Traffic via Gap Junctions Reinforces Lomustine-Induced Toxicity in Glioblastoma Independent of MGMT Promoter Methylation Status
Glioblastoma is a malignant brain tumor and one of the most lethal cancers in human. Temozolomide constitutes the standard chemotherapeutic agent, but only shows limited efficacy in glioblastoma patients with unmethylated O-6-methylguanine-DNA methyltransferase (MGMT) promoter status. Recently, it h...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997332/ https://www.ncbi.nlm.nih.gov/pubmed/33673490 http://dx.doi.org/10.3390/ph14030195 |
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author | Schneider, Matthias Potthoff, Anna-Laura Evert, Bernd O. Dicks, Marius Ehrentraut, Denise Dolf, Andreas Schmidt, Elena N. C. Schäfer, Niklas Borger, Valeri Pietsch, Torsten Westhoff, Mike-Andrew Güresir, Erdem Waha, Andreas Vatter, Hartmut Heiland, Dieter H. Schuss, Patrick Herrlinger, Ulrich |
author_facet | Schneider, Matthias Potthoff, Anna-Laura Evert, Bernd O. Dicks, Marius Ehrentraut, Denise Dolf, Andreas Schmidt, Elena N. C. Schäfer, Niklas Borger, Valeri Pietsch, Torsten Westhoff, Mike-Andrew Güresir, Erdem Waha, Andreas Vatter, Hartmut Heiland, Dieter H. Schuss, Patrick Herrlinger, Ulrich |
author_sort | Schneider, Matthias |
collection | PubMed |
description | Glioblastoma is a malignant brain tumor and one of the most lethal cancers in human. Temozolomide constitutes the standard chemotherapeutic agent, but only shows limited efficacy in glioblastoma patients with unmethylated O-6-methylguanine-DNA methyltransferase (MGMT) promoter status. Recently, it has been shown that glioblastoma cells communicate via particular ion-channels—so-called gap junctions. Interestingly, inhibition of these ion channels has been reported to render MGMT promoter-methylated glioblastoma cells more susceptible for a therapy with temozolomide. However, given the percentage of about 65% of glioblastoma patients with an unmethylated MGMT promoter methylation status, this treatment strategy is limited to only a minority of glioblastoma patients. In the present study we show that—in contrast to temozolomide—pharmacological inhibition of intercellular cytosolic traffic via gap junctions reinforces the antitumoral effects of chemotherapeutic agent lomustine, independent of MGMT promoter methylation status. In view of the growing interest of lomustine in glioblastoma first and second line therapy, these findings might provide a clinically-feasible way to profoundly augment chemotherapeutic effects for all glioblastoma patients. |
format | Online Article Text |
id | pubmed-7997332 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-79973322021-03-27 Inhibition of Intercellular Cytosolic Traffic via Gap Junctions Reinforces Lomustine-Induced Toxicity in Glioblastoma Independent of MGMT Promoter Methylation Status Schneider, Matthias Potthoff, Anna-Laura Evert, Bernd O. Dicks, Marius Ehrentraut, Denise Dolf, Andreas Schmidt, Elena N. C. Schäfer, Niklas Borger, Valeri Pietsch, Torsten Westhoff, Mike-Andrew Güresir, Erdem Waha, Andreas Vatter, Hartmut Heiland, Dieter H. Schuss, Patrick Herrlinger, Ulrich Pharmaceuticals (Basel) Article Glioblastoma is a malignant brain tumor and one of the most lethal cancers in human. Temozolomide constitutes the standard chemotherapeutic agent, but only shows limited efficacy in glioblastoma patients with unmethylated O-6-methylguanine-DNA methyltransferase (MGMT) promoter status. Recently, it has been shown that glioblastoma cells communicate via particular ion-channels—so-called gap junctions. Interestingly, inhibition of these ion channels has been reported to render MGMT promoter-methylated glioblastoma cells more susceptible for a therapy with temozolomide. However, given the percentage of about 65% of glioblastoma patients with an unmethylated MGMT promoter methylation status, this treatment strategy is limited to only a minority of glioblastoma patients. In the present study we show that—in contrast to temozolomide—pharmacological inhibition of intercellular cytosolic traffic via gap junctions reinforces the antitumoral effects of chemotherapeutic agent lomustine, independent of MGMT promoter methylation status. In view of the growing interest of lomustine in glioblastoma first and second line therapy, these findings might provide a clinically-feasible way to profoundly augment chemotherapeutic effects for all glioblastoma patients. MDPI 2021-02-27 /pmc/articles/PMC7997332/ /pubmed/33673490 http://dx.doi.org/10.3390/ph14030195 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ). |
spellingShingle | Article Schneider, Matthias Potthoff, Anna-Laura Evert, Bernd O. Dicks, Marius Ehrentraut, Denise Dolf, Andreas Schmidt, Elena N. C. Schäfer, Niklas Borger, Valeri Pietsch, Torsten Westhoff, Mike-Andrew Güresir, Erdem Waha, Andreas Vatter, Hartmut Heiland, Dieter H. Schuss, Patrick Herrlinger, Ulrich Inhibition of Intercellular Cytosolic Traffic via Gap Junctions Reinforces Lomustine-Induced Toxicity in Glioblastoma Independent of MGMT Promoter Methylation Status |
title | Inhibition of Intercellular Cytosolic Traffic via Gap Junctions Reinforces Lomustine-Induced Toxicity in Glioblastoma Independent of MGMT Promoter Methylation Status |
title_full | Inhibition of Intercellular Cytosolic Traffic via Gap Junctions Reinforces Lomustine-Induced Toxicity in Glioblastoma Independent of MGMT Promoter Methylation Status |
title_fullStr | Inhibition of Intercellular Cytosolic Traffic via Gap Junctions Reinforces Lomustine-Induced Toxicity in Glioblastoma Independent of MGMT Promoter Methylation Status |
title_full_unstemmed | Inhibition of Intercellular Cytosolic Traffic via Gap Junctions Reinforces Lomustine-Induced Toxicity in Glioblastoma Independent of MGMT Promoter Methylation Status |
title_short | Inhibition of Intercellular Cytosolic Traffic via Gap Junctions Reinforces Lomustine-Induced Toxicity in Glioblastoma Independent of MGMT Promoter Methylation Status |
title_sort | inhibition of intercellular cytosolic traffic via gap junctions reinforces lomustine-induced toxicity in glioblastoma independent of mgmt promoter methylation status |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997332/ https://www.ncbi.nlm.nih.gov/pubmed/33673490 http://dx.doi.org/10.3390/ph14030195 |
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