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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.

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.

journal_name

Pharm Biol

journal_title

Pharmaceutical biology

authors

Cao WQ,Zhai XQ,Ma JW,Fu XQ,Zhao BS,Zhang P,Fu XY

doi

10.1080/13880209.2019.1703756

subject

Has Abstract

pub_date

2020-12-01 00:00:00

pages

72-79

issue

eissn

1388-0209

issn

1744-5116

journal_volume

pub_type

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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.