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Osthole induces necroptosis via ROS overproduction in glioma cells
Glioma is a common primary malignant tumor that has a poor prognosis and often develops drug resistance. The coumarin derivative osthole has previously been reported to induce cancer cell apoptosis. Recently, we found that it could also trigger glioma cell necroptosis, a type of cell death that is u...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876487/ https://www.ncbi.nlm.nih.gov/pubmed/33350608 http://dx.doi.org/10.1002/2211-5463.13069 |
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author | Huangfu, Mengjie Wei, Riming Wang, Juan Qin, Jianli Yu, Dan Guan, Xiao Li, Xumei Fu, Minglei Liu, Haiping Chen, Xu |
author_facet | Huangfu, Mengjie Wei, Riming Wang, Juan Qin, Jianli Yu, Dan Guan, Xiao Li, Xumei Fu, Minglei Liu, Haiping Chen, Xu |
author_sort | Huangfu, Mengjie |
collection | PubMed |
description | Glioma is a common primary malignant tumor that has a poor prognosis and often develops drug resistance. The coumarin derivative osthole has previously been reported to induce cancer cell apoptosis. Recently, we found that it could also trigger glioma cell necroptosis, a type of cell death that is usually accompanied with reactive oxygen species (ROS) production. However, the relationship between ROS production and necroptosis induced by osthole has not been fully elucidated. In this study, we found that osthole could induce necroptosis of glioma cell lines U87 and C6; such cell death was distinct from apoptosis induced by MG‐132. Expression of necroptosis inhibitor caspase‐8 was decreased, and levels of necroptosis proteins receptor‐interacting protein 1 (RIP1), RIP3 and mixed lineage kinase domain‐like protein were increased in U87 and C6 cells after treatment with osthole, whereas levels of apoptosis‐related proteins caspase‐3, caspase‐7, and caspase‐9 were not increased. Lactate dehydrogenase release and flow cytometry assays confirmed that cell death induced by osthole was primarily necrosis. In addition, necroptosis induced by osthole was accompanied by excessive production of ROS, as observed for other necroptosis‐inducing reagents. Pretreatment with the RIP1 inhibitor necrostatin‐1 attenuated both osthole‐induced necroptosis and the production of ROS in U87 cells. Furthermore, the ROS inhibitor N‐acetylcysteine decreased osthole‐induced necroptosis and growth inhibition. Overall, these findings suggest that osthole induces necroptosis of glioma cells via ROS production and thus may have potential for development into a therapeutic drug for glioma therapy. |
format | Online Article Text |
id | pubmed-7876487 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-78764872021-02-18 Osthole induces necroptosis via ROS overproduction in glioma cells Huangfu, Mengjie Wei, Riming Wang, Juan Qin, Jianli Yu, Dan Guan, Xiao Li, Xumei Fu, Minglei Liu, Haiping Chen, Xu FEBS Open Bio Research Articles Glioma is a common primary malignant tumor that has a poor prognosis and often develops drug resistance. The coumarin derivative osthole has previously been reported to induce cancer cell apoptosis. Recently, we found that it could also trigger glioma cell necroptosis, a type of cell death that is usually accompanied with reactive oxygen species (ROS) production. However, the relationship between ROS production and necroptosis induced by osthole has not been fully elucidated. In this study, we found that osthole could induce necroptosis of glioma cell lines U87 and C6; such cell death was distinct from apoptosis induced by MG‐132. Expression of necroptosis inhibitor caspase‐8 was decreased, and levels of necroptosis proteins receptor‐interacting protein 1 (RIP1), RIP3 and mixed lineage kinase domain‐like protein were increased in U87 and C6 cells after treatment with osthole, whereas levels of apoptosis‐related proteins caspase‐3, caspase‐7, and caspase‐9 were not increased. Lactate dehydrogenase release and flow cytometry assays confirmed that cell death induced by osthole was primarily necrosis. In addition, necroptosis induced by osthole was accompanied by excessive production of ROS, as observed for other necroptosis‐inducing reagents. Pretreatment with the RIP1 inhibitor necrostatin‐1 attenuated both osthole‐induced necroptosis and the production of ROS in U87 cells. Furthermore, the ROS inhibitor N‐acetylcysteine decreased osthole‐induced necroptosis and growth inhibition. Overall, these findings suggest that osthole induces necroptosis of glioma cells via ROS production and thus may have potential for development into a therapeutic drug for glioma therapy. John Wiley and Sons Inc. 2021-01-19 /pmc/articles/PMC7876487/ /pubmed/33350608 http://dx.doi.org/10.1002/2211-5463.13069 Text en © 2020 The Authors. FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Huangfu, Mengjie Wei, Riming Wang, Juan Qin, Jianli Yu, Dan Guan, Xiao Li, Xumei Fu, Minglei Liu, Haiping Chen, Xu Osthole induces necroptosis via ROS overproduction in glioma cells |
title | Osthole induces necroptosis via ROS overproduction in glioma cells |
title_full | Osthole induces necroptosis via ROS overproduction in glioma cells |
title_fullStr | Osthole induces necroptosis via ROS overproduction in glioma cells |
title_full_unstemmed | Osthole induces necroptosis via ROS overproduction in glioma cells |
title_short | Osthole induces necroptosis via ROS overproduction in glioma cells |
title_sort | osthole induces necroptosis via ros overproduction in glioma cells |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876487/ https://www.ncbi.nlm.nih.gov/pubmed/33350608 http://dx.doi.org/10.1002/2211-5463.13069 |
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