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Updated: Nov 5, 2025
The Clinical Application of Tumor Treating Fields Therapy in Glioblastoma
Published on: April 16, 2019
Application of the antitussive agents oxelaidin and butamirate as anti-glioma agents
Sook-Ja Lee1, Seon-Yong Yeom1, Jee-Young Lee2
1Research Institute for Future Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Irwon-dong, Seoul, 06351, Korea.
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.
Insights
Oxelaidin and butamirate, repurposed cough suppressants, show promise in treating glioblastoma by inhibiting tumor growth and STAT3 signaling. These non-toxic agents effectively reduced glioblastoma in mouse models, suggesting potential as novel cancer therapies.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Glioblastoma (GBM) is an aggressive brain tumor known for relapse and chemotherapy resistance.
- Current treatments lack non-toxic agents effective against GBM.
- Ras-related associated with diabetes (RRAD) protein activates STAT3, crucial for cancer cell survival.
Purpose of the Study:
- Identify safe and effective non-toxic agents for GBM treatment.
- Investigate the anti-tumor effects of FDA-approved drugs on GBM.
- Elucidate the mechanism of action for identified GBM inhibitors.
Main Methods:
- High-throughput screening of FDA-approved drugs against GBM cell lines (LN229, U87, T98G).
- Assessed drug effects on cell proliferation and RRAD-dependent pathways.
- Utilized docking simulations to analyze drug-protein interactions.
- Evaluated drug efficacy in a glioblastoma xenograft mouse model.
Main Results:
- Oxelaidin and butamirate inhibited GBM cell growth, particularly in RRAD-positive cells.
- These drugs suppressed STAT3 transcriptional activity, down-regulating cyclin D1 and survivin.
- Oxelaidin treatment inhibited RRAD-associated signaling cascades (p-EGFR, p-Akt, p-STAT3).
- Oxelaidin and butamirate significantly suppressed tumor growth in vivo without adverse effects.
Conclusions:
- Oxelaidin and butamirate demonstrate significant anti-tumor activity against glioblastoma.
- These drugs represent potential novel therapeutic candidates for glioblastoma treatment.
- The mechanism involves the inhibition of STAT3 signaling pathways.
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