Natural borneol sensitizes human glioma cells to cisplatin-induced apoptosis by triggering ROS-mediated oxidative damage and regulation of MAPKs and PI3K/AKT pathway

Autor: Bai-song Zhao, Xiao-yan Fu, Pu Zhang, Xueqi Fu, Xiao-qian Zhai, Wen-qiang Cao, Ji-wei Ma
Rok vydání: 2019
Předmět:
MAPK/ERK pathway
p53
DNA damage
Cell Survival
medicine.medical_treatment
Pharmaceutical Science
Antineoplastic Agents
Apoptosis
RM1-950
030226 pharmacology & pharmacy
01 natural sciences
03 medical and health sciences
0302 clinical medicine
Cell Line
Tumor
Drug Discovery
medicine
Humans
Protein kinase B
PI3K/AKT/mTOR pathway
Pharmacology
chemistry.chemical_classification
Cisplatin
reactive oxygen species
Reactive oxygen species
Chemotherapy
Camphanes
Dose-Response Relationship
Drug
Chemistry
Akt
General Medicine
Glioma
0104 chemical sciences
010404 medicinal & biomolecular chemistry
Oxidative Stress
ERK
Complementary and alternative medicine
Drug Resistance
Neoplasm
Cancer research
Molecular Medicine
Therapeutics. Pharmacology
Chemo-sensitization
Phosphatidylinositol 3-Kinase
Proto-Oncogene Proteins c-akt
medicine.drug
Research Article
Zdroj: Pharmaceutical Biology
Pharmaceutical Biology, Vol 58, Iss 1, Pp 72-79 (2020)
ISSN: 1744-5116
Popis: 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.
Databáze: OpenAIRE
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