Abstract

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.

Details

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
Author
Wen-qiang Cao 1 ; Xiao-qian Zhai 2 ; Ji-wei, Ma 3 ; Xue-qi, Fu 4 ; Bai-song, Zhao 5 ; Zhang, Pu 6   VIAFID ORCID Logo  ; Xiao-yan, Fu 7 

1  School of Life Sciences, Jilin University, Changchun, China; Department of Biotechnology, Zhuhai Hopegenes Medical & Phamaceutical Institute, Zhuhai, China 
2  Department of Pathology, The Second Affiliated Hospital of Shandong First Medical University, Taian, China 
3  Department of Pathology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China 
4  School of Life Sciences, Jilin University, Changchun, China 
5  Department of Biotechnology, Zhuhai Hopegenes Medical & Phamaceutical Institute, Zhuhai, China 
6  Department of Cardiology, The Central Hospital of Taian, Taian, China 
7  School of Basic Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, China 
Pages
72-79
Publication year
2020
Publication date
Dec 2020
Publisher
Taylor & Francis Ltd.
ISSN
13880209
e-ISSN
17445116
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1080/13880209.2019.1703756
ProQuest document ID
2509433547
Copyright
© 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This work is licensed under the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.