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 met...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2020-01-01
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| Series: | Pharmaceutical Biology |
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| Online Access: | http://dx.doi.org/10.1080/13880209.2019.1703756 |
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| author | Wen-qiang Cao Xiao-qian Zhai Ji-wei Ma Xue-qi Fu Bai-song Zhao Pu Zhang Xiao-yan Fu |
| author_facet | Wen-qiang Cao Xiao-qian Zhai Ji-wei Ma Xue-qi Fu Bai-song Zhao Pu Zhang Xiao-yan Fu |
| author_sort | Wen-qiang Cao |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-17T07:04:42Z |
| format | Article |
| id | doaj.art-696db52a619849a1a6b90c59e5c91d87 |
| institution | Directory Open Access Journal |
| issn | 1388-0209 1744-5116 |
| language | English |
| last_indexed | 2024-12-17T07:04:42Z |
| publishDate | 2020-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Pharmaceutical Biology |
| spelling | doaj.art-696db52a619849a1a6b90c59e5c91d872022-12-21T21:59:13ZengTaylor & Francis GroupPharmaceutical Biology1388-02091744-51162020-01-01581727910.1080/13880209.2019.17037561703756Natural borneol sensitizes human glioma cells to cisplatin-induced apoptosis by triggering ROS-mediated oxidative damage and regulation of MAPKs and PI3K/AKT pathwayWen-qiang Cao0Xiao-qian Zhai1Ji-wei Ma2Xue-qi Fu3Bai-song Zhao4Pu Zhang5Xiao-yan Fu6School of Life Sciences, Jilin UniversityDepartment of Pathology, The Second Affiliated Hospital of Shandong First Medical UniversityDepartment of Pathology, Shandong Provincial Hospital Affiliated to Shandong UniversitySchool of Life Sciences, Jilin UniversityDepartment of Biotechnology, Zhuhai Hopegenes Medical & Phamaceutical InstituteDepartment of Cardiology, The Central Hospital of TaianSchool of Basic Medicine, Shandong First Medical University & Shandong Academy of Medical SciencesContext 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.http://dx.doi.org/10.1080/13880209.2019.1703756chemo-sensitizationdna damagereactive oxygen speciesp53erkakt |
| spellingShingle | Wen-qiang Cao Xiao-qian Zhai Ji-wei Ma Xue-qi Fu Bai-song Zhao Pu Zhang Xiao-yan Fu Natural borneol sensitizes human glioma cells to cisplatin-induced apoptosis by triggering ROS-mediated oxidative damage and regulation of MAPKs and PI3K/AKT pathway Pharmaceutical Biology chemo-sensitization dna damage reactive oxygen species p53 erk akt |
| 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 | chemo-sensitization dna damage reactive oxygen species p53 erk akt |
| url | http://dx.doi.org/10.1080/13880209.2019.1703756 |
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