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Natural borneol sensitizes human glioma cells to cisplatin-induced apoptosis by triggering ROS-mediated oxidative damage and regulation of MAPKs and PI3K/AKT pathway
CONTEXT: Cisplatin-based chemotherapy was widely used in treating human malignancies. However, side effects and chemoresistance remains the major obstacle. OBJECTIVE: To verify whether natural borneol (NB) can enhance cisplatin-induced glioma cell apoptosis and explore the mechanism. MATERIALS AND M...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6970185/ https://www.ncbi.nlm.nih.gov/pubmed/31875760 http://dx.doi.org/10.1080/13880209.2019.1703756 |
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author | Cao, Wen-qiang Zhai, Xiao-qian Ma, Ji-wei Fu, Xue-qi Zhao, Bai-song Zhang, Pu Fu, Xiao-yan |
author_facet | Cao, Wen-qiang Zhai, Xiao-qian Ma, Ji-wei Fu, Xue-qi Zhao, Bai-song Zhang, Pu Fu, Xiao-yan |
author_sort | Cao, Wen-qiang |
collection | PubMed |
description | CONTEXT: Cisplatin-based chemotherapy was widely used in treating human malignancies. However, side effects and chemoresistance remains the major obstacle. OBJECTIVE: To verify whether natural borneol (NB) can enhance cisplatin-induced glioma cell apoptosis and explore the mechanism. MATERIALS AND METHODS: Cytotoxicity of cisplatin and/or NB towards U251 and U87 cells were determined with the MTT assay. Cells were treated with 0.25–80 μg/mL cisplatin and/or 5–80 μM NB for 48 h. The effects of NB and/or cisplatin on apoptosis and cell cycle distribution were quantified by flow cytometric analysis. Protein expression was detected by western blotting. ROS generation was conducted by measuring and visualising an oxidation-sensitive fluorescein DCFH-DA. RESULTS: NB synergistically enhanced the anticancer efficacy of cisplatin in human glioma cells. Co-treatment of 40 μg/mL NB and 40 μg/mL cisplatin significantly inhibited U251 cell viability from 100% to 28.2% and increased the sub-G1 population from 1.4% to 59.3%. Further detection revealed that NB enhanced cisplatin-induced apoptosis by activating caspases and triggering reactive oxygen species (ROS) overproduction as evidenced by the enhancement of green fluorescence intensity from 265% to 645%. ROS-mediated DNA damage was observed as reflected by the activation of ATM/ATR, p53 and histone. Moreover, MAPKs and PI3K/AKT pathways also contributed to co-treatment-induced U251 cell growth inhibition. ROS inhibition by antioxidants effectively improved MAPKs and PI3K/AKT functions and cell viability, indicating that NB enhanced cisplatin-induced cell growth in a ROS-dependent manner. DISCUSSION AND CONCLUSIONS: Natural borneol had the potential to sensitise human glioma cells to cisplatin-induced apoptosis with potential application in the clinic. |
format | Online Article Text |
id | pubmed-6970185 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-69701852020-01-31 Natural borneol sensitizes human glioma cells to cisplatin-induced apoptosis by triggering ROS-mediated oxidative damage and regulation of MAPKs and PI3K/AKT pathway Cao, Wen-qiang Zhai, Xiao-qian Ma, Ji-wei Fu, Xue-qi Zhao, Bai-song Zhang, Pu Fu, Xiao-yan Pharm Biol Research Article CONTEXT: Cisplatin-based chemotherapy was widely used in treating human malignancies. However, side effects and chemoresistance remains the major obstacle. OBJECTIVE: To verify whether natural borneol (NB) can enhance cisplatin-induced glioma cell apoptosis and explore the mechanism. MATERIALS AND METHODS: Cytotoxicity of cisplatin and/or NB towards U251 and U87 cells were determined with the MTT assay. Cells were treated with 0.25–80 μg/mL cisplatin and/or 5–80 μM NB for 48 h. The effects of NB and/or cisplatin on apoptosis and cell cycle distribution were quantified by flow cytometric analysis. Protein expression was detected by western blotting. ROS generation was conducted by measuring and visualising an oxidation-sensitive fluorescein DCFH-DA. RESULTS: NB synergistically enhanced the anticancer efficacy of cisplatin in human glioma cells. Co-treatment of 40 μg/mL NB and 40 μg/mL cisplatin significantly inhibited U251 cell viability from 100% to 28.2% and increased the sub-G1 population from 1.4% to 59.3%. Further detection revealed that NB enhanced cisplatin-induced apoptosis by activating caspases and triggering reactive oxygen species (ROS) overproduction as evidenced by the enhancement of green fluorescence intensity from 265% to 645%. ROS-mediated DNA damage was observed as reflected by the activation of ATM/ATR, p53 and histone. Moreover, MAPKs and PI3K/AKT pathways also contributed to co-treatment-induced U251 cell growth inhibition. ROS inhibition by antioxidants effectively improved MAPKs and PI3K/AKT functions and cell viability, indicating that NB enhanced cisplatin-induced cell growth in a ROS-dependent manner. DISCUSSION AND CONCLUSIONS: Natural borneol had the potential to sensitise human glioma cells to cisplatin-induced apoptosis with potential application in the clinic. Taylor & Francis 2019-12-26 /pmc/articles/PMC6970185/ /pubmed/31875760 http://dx.doi.org/10.1080/13880209.2019.1703756 Text en © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Cao, Wen-qiang Zhai, Xiao-qian Ma, Ji-wei Fu, Xue-qi Zhao, Bai-song Zhang, Pu Fu, Xiao-yan Natural borneol sensitizes human glioma cells to cisplatin-induced apoptosis by triggering ROS-mediated oxidative damage and regulation of MAPKs and PI3K/AKT pathway |
title | Natural borneol sensitizes human glioma cells to cisplatin-induced apoptosis by triggering ROS-mediated oxidative damage and regulation of MAPKs and PI3K/AKT pathway |
title_full | Natural borneol sensitizes human glioma cells to cisplatin-induced apoptosis by triggering ROS-mediated oxidative damage and regulation of MAPKs and PI3K/AKT pathway |
title_fullStr | Natural borneol sensitizes human glioma cells to cisplatin-induced apoptosis by triggering ROS-mediated oxidative damage and regulation of MAPKs and PI3K/AKT pathway |
title_full_unstemmed | Natural borneol sensitizes human glioma cells to cisplatin-induced apoptosis by triggering ROS-mediated oxidative damage and regulation of MAPKs and PI3K/AKT pathway |
title_short | Natural borneol sensitizes human glioma cells to cisplatin-induced apoptosis by triggering ROS-mediated oxidative damage and regulation of MAPKs and PI3K/AKT pathway |
title_sort | natural borneol sensitizes human glioma cells to cisplatin-induced apoptosis by triggering ros-mediated oxidative damage and regulation of mapks and pi3k/akt pathway |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6970185/ https://www.ncbi.nlm.nih.gov/pubmed/31875760 http://dx.doi.org/10.1080/13880209.2019.1703756 |
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