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Cedrus atlantica Extract Suppress Glioblastoma Growth through Promotion of Genotoxicity and Apoptosis: In Vitro and In Vivo Studies
Glioblastoma (GBM) is the most common malignant primary brain tumor in humans, exhibiting highly infiltrative growth and drug resistance to conventional chemotherapy. Cedrus atlantica (CAt) extract has been shown to decrease postoperative pain and inhibit the growth of K562 leukemia cells. The aim o...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Ivyspring International Publisher
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100640/ https://www.ncbi.nlm.nih.gov/pubmed/33967620 http://dx.doi.org/10.7150/ijms.54468 |
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author | Chang, Kai-Fu Chang, Jinghua Tsai Huang, Xiao-Fan Huang, Ya-Chih Li, Chia-Yu Weng, Jun-Cheng Hsiao, Chih-Yen Hsu, Hui-Ju Tsai, Nu-Man |
author_facet | Chang, Kai-Fu Chang, Jinghua Tsai Huang, Xiao-Fan Huang, Ya-Chih Li, Chia-Yu Weng, Jun-Cheng Hsiao, Chih-Yen Hsu, Hui-Ju Tsai, Nu-Man |
author_sort | Chang, Kai-Fu |
collection | PubMed |
description | Glioblastoma (GBM) is the most common malignant primary brain tumor in humans, exhibiting highly infiltrative growth and drug resistance to conventional chemotherapy. Cedrus atlantica (CAt) extract has been shown to decrease postoperative pain and inhibit the growth of K562 leukemia cells. The aim of this study was to assess the anti-GBM activity and molecular mechanism of CAt extract in vitro and in vivo. The results showed that CAt extract greatly suppressed GBM cells both in vitro and in vivo and enhanced the survival rate in subcutaneous and orthotopic animal models. Moreover, CAt extract increased the level of ROS and induced DNA damage, resulting in cell cycle arrest at the G(0)/G(1) phase and cell apoptosis. Western blotting results indicated that CAt extract regulates p53/p21 and CDK4/cyclin D1 protein expression and activates extrinsic and intrinsic apoptosis. Furthermore, CAt extract enhanced the cytotoxicity of Temozolomide and decreased AKT/mTOR signaling by combination treatment. In toxicity assays, CAt extract exhibited low cytotoxicity toward normal cells or organs in vitro and in vivo. CAt extract suppresses the growth of GBM by induction of genotoxicity and activation of apoptosis. The results of this study suggest that CAt extract can be developed as a therapeutic agent or adjuvant for GBM treatment in the future. |
format | Online Article Text |
id | pubmed-8100640 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-81006402021-05-06 Cedrus atlantica Extract Suppress Glioblastoma Growth through Promotion of Genotoxicity and Apoptosis: In Vitro and In Vivo Studies Chang, Kai-Fu Chang, Jinghua Tsai Huang, Xiao-Fan Huang, Ya-Chih Li, Chia-Yu Weng, Jun-Cheng Hsiao, Chih-Yen Hsu, Hui-Ju Tsai, Nu-Man Int J Med Sci Research Paper Glioblastoma (GBM) is the most common malignant primary brain tumor in humans, exhibiting highly infiltrative growth and drug resistance to conventional chemotherapy. Cedrus atlantica (CAt) extract has been shown to decrease postoperative pain and inhibit the growth of K562 leukemia cells. The aim of this study was to assess the anti-GBM activity and molecular mechanism of CAt extract in vitro and in vivo. The results showed that CAt extract greatly suppressed GBM cells both in vitro and in vivo and enhanced the survival rate in subcutaneous and orthotopic animal models. Moreover, CAt extract increased the level of ROS and induced DNA damage, resulting in cell cycle arrest at the G(0)/G(1) phase and cell apoptosis. Western blotting results indicated that CAt extract regulates p53/p21 and CDK4/cyclin D1 protein expression and activates extrinsic and intrinsic apoptosis. Furthermore, CAt extract enhanced the cytotoxicity of Temozolomide and decreased AKT/mTOR signaling by combination treatment. In toxicity assays, CAt extract exhibited low cytotoxicity toward normal cells or organs in vitro and in vivo. CAt extract suppresses the growth of GBM by induction of genotoxicity and activation of apoptosis. The results of this study suggest that CAt extract can be developed as a therapeutic agent or adjuvant for GBM treatment in the future. Ivyspring International Publisher 2021-04-22 /pmc/articles/PMC8100640/ /pubmed/33967620 http://dx.doi.org/10.7150/ijms.54468 Text en © The author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper Chang, Kai-Fu Chang, Jinghua Tsai Huang, Xiao-Fan Huang, Ya-Chih Li, Chia-Yu Weng, Jun-Cheng Hsiao, Chih-Yen Hsu, Hui-Ju Tsai, Nu-Man Cedrus atlantica Extract Suppress Glioblastoma Growth through Promotion of Genotoxicity and Apoptosis: In Vitro and In Vivo Studies |
title | Cedrus atlantica Extract Suppress Glioblastoma Growth through Promotion of Genotoxicity and Apoptosis: In Vitro and In Vivo Studies |
title_full | Cedrus atlantica Extract Suppress Glioblastoma Growth through Promotion of Genotoxicity and Apoptosis: In Vitro and In Vivo Studies |
title_fullStr | Cedrus atlantica Extract Suppress Glioblastoma Growth through Promotion of Genotoxicity and Apoptosis: In Vitro and In Vivo Studies |
title_full_unstemmed | Cedrus atlantica Extract Suppress Glioblastoma Growth through Promotion of Genotoxicity and Apoptosis: In Vitro and In Vivo Studies |
title_short | Cedrus atlantica Extract Suppress Glioblastoma Growth through Promotion of Genotoxicity and Apoptosis: In Vitro and In Vivo Studies |
title_sort | cedrus atlantica extract suppress glioblastoma growth through promotion of genotoxicity and apoptosis: in vitro and in vivo studies |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100640/ https://www.ncbi.nlm.nih.gov/pubmed/33967620 http://dx.doi.org/10.7150/ijms.54468 |
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