Back to Search
Start Over
Application of the antitussive agents oxelaidin and butamirate as anti-glioma agents
- Source :
- Scientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
- Publication Year :
- 2021
- Publisher :
- Nature Portfolio, 2021.
-
Abstract
- Glioblastoma (GBM) is an aggressive brain tumor with a strong tendency of relapse and resistance to chemotherapy, but we currently lack non-toxic agents that effectively treat GBM. In this study, high-throughput screening of FDA-approved drugs was performed to identify safe and effective molecules and test their effect on GBM cell lines, LN229, U87 and T98G. Cough suppressants, oxelaidin and butamirate inhibited GBM growth. A Ras family GTPase, Ras-related associated with diabetes (RRAD), contributes to activation of STAT3, which is essential for survival and growth of many cancer types. Interestingly, oxelaidin and butamirate did not affect proliferation in RRAD negative GBM cells. Docking simulation analyses revealed selective interactions between oxelaidin and RRAD. The mechanism by which butamirate and oxelaidin inhibits GBM cell growth involves the suppression of STAT3 transcriptional activity, leading to down-regulation of cyclin D1 and survivin. In addition, components of RRAD-associated signaling cascades, including p-EGFR, p-Akt, and p-STAT3, were inhibited upon oxelaidin treatment. Intraperitoneal administration of oxelaidin or butamirate markedly suppressed tumor growth in a glioblastoma xenograft mouse model without significant adverse effects. Our collective findings indicate that oxelaidin and butamirate exert anti-tumor effects in glioblastoma, supporting its utility as a novel therapeutic candidate for glioblastoma.
- Subjects :
- Models, Molecular
STAT3 Transcription Factor
Science
Antineoplastic Agents
Apoptosis
Mice
Structure-Activity Relationship
Cyclin D1
Cell Line, Tumor
Glioma
Survivin
medicine
Animals
Humans
U87
STAT3
Cell Proliferation
Binding Sites
Multidisciplinary
Dose-Response Relationship, Drug
biology
Cell growth
business.industry
Drug Repositioning
Cancer
medicine.disease
Phenylbutyrates
Xenograft Model Antitumor Assays
nervous system diseases
ErbB Receptors
Gene Expression Regulation, Neoplastic
Antitussive Agents
Disease Models, Animal
Cell culture
biology.protein
Cancer research
Medicine
Drug Screening Assays, Antitumor
business
Protein Binding
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 20452322
- Volume :
- 11
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....8171566ae4848988409b982adf3921ba