A steroidal saponin form Paris vietnamensis (Takht.) reverses temozolomide resistance in glioblastoma cells via inducing apoptosis through ROS/PI3K/Akt pathway
| Autor: | Fei Fang, Peng-Cheng Qiu, Yun-Yang Lu, Yu-Qiang Ji, Shan Zhang, Hua Li, Hai-Feng Tang |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
chemistry.chemical_classification
Reactive oxygen species Health (social science) TUNEL assay Temozolomide medicine.diagnostic_test Chemistry General Medicine General Biochemistry Genetics and Molecular Biology Flow cytometry 03 medical and health sciences 0302 clinical medicine Terminal deoxynucleotidyl transferase Apoptosis 030220 oncology & carcinogenesis medicine Cancer research 030211 gastroenterology & hepatology Protein kinase B PI3K/AKT/mTOR pathway medicine.drug |
| Zdroj: | BioScience Trends. 14:123-133 |
| ISSN: | 1881-7823 1881-7815 |
| DOI: | 10.5582/bst.2020.01005 |
| Popis: | Glioblastoma is one of the most difficult cancers to treat with a 5-year overall survival rate less than 5%. Temozolomide (TMZ) is an effective drug for prolonging the overall survival time of patients, while drug-resistance is an important clinical problem at present. Pennogenin-3-α-L-rhamnopyranosyl-(1→4)-[α-Lrhamno-pyranosyl-(1→2)]- β-D-glucopyranoside (N45), a steroidal saponin, was isolated from the rhizomes of Paris vietnamensis (Takht.), which is used as a Traditional Chinese Medicine and has been reported to possess preclinical anticancer efficacy in various cancer types. However, the mechanism of the inhibition of N45 on glioblastoma cells and its possible application in the treatment of chemotherapy-resistant glioblastoma cells are still unknown. In this study, we use cellular methodological experiments including cell counting kit-8 (CCK-8) assay, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining assay, flow cytometry assay, transmission electron microscopy (TEM) and Western blot. The results show that N45 significantly suppresses the proliferation of glioblastoma cells and TMZ-resistant glioblastoma cells (U87R) by inducing mitochondrial apoptosis through reactive oxygen species (ROS)/phosphoinositide 3-kinase (PI3K)/Akt signal pathway, and the N-acetyl-L-cysteine (NAC) combined with N45 effectively reduced N45-mediated apoptosis and reversed the inhibition of PI3K/Akt signal pathway. In addition, N45 decreased the drug-resistance by down-regulation of nuclear factor kappa-B p65 (NF-κB p65) to attenuate O6-methylguanine-DNA methyltransferase (MGMT) in TMZ-resistant glioblastoma cells (U87R). Our findings proved that N45 might be a potential therapeutic agent against glioblastoma and TMZ-resistant glioblastoma, promising to be a potential agent to reduce drug resistance. |
| Databáze: | OpenAIRE |
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