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Amantadine against glioma via ROS-mediated apoptosis and autophagy arrest
Yusong Luo1,2, Ruolan Liu1,2, He Zhang1,2
1Department of Neurosurgery, the Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, China.
Abstract:
Glioma is a common primary nervous system malignant tumor with poor overall cure rate and low survival rate, yet successful treatment still remains a challenge. Here, we demonstrated that amantadine (AMT) exhibits the powerful anti-glioma effect by promoting apoptosis and autophagy in vivo and in vitro. Mechanistically, amantadine induces a large amount of reactive oxygen species (ROS) accumulation in glioma cells, and then triggers apoptosis by destroying mitochondria. In addition, amantadine induces the initiation of autophagy and inhibits the fusion of autophagosome and lysosome, consequently performing an anti-glioma role. Taken together, our findings suggest that amantadine could be a promising anti-glioma drug that inhibits glioma cells by inducing apoptosis and autophagy, which may provide a novel potential treatment option for patients.
Insights
Amantadine (AMT) shows significant anti-glioma effects by inducing cancer cell death through apoptosis and autophagy. This research highlights AMT as a potential new treatment for glioma patients.
Area of Science:
- Neuro-oncology
- Molecular Biology
- Pharmacology
Background:
- Glioma is a prevalent malignant brain tumor with a low survival rate.
- Current treatments for glioma face significant challenges, necessitating novel therapeutic strategies.
Purpose of the Study:
- To investigate the anti-glioma potential of amantadine (AMT).
- To elucidate the mechanisms by which AMT exerts its anti-glioma effects, focusing on apoptosis and autophagy.
Main Methods:
- In vitro and in vivo experiments were conducted.
- Assessed the impact of amantadine on glioma cell apoptosis and autophagy.
- Investigated the role of reactive oxygen species (ROS) and mitochondrial damage.
Main Results:
- Amantadine effectively inhibited glioma cell growth both in vitro and in vivo.
- AMT induced significant apoptosis by increasing ROS and damaging mitochondria.
- Amantadine promoted autophagy initiation while inhibiting autophagosome-lysosome fusion.
Conclusions:
- Amantadine demonstrates potent anti-glioma activity by concurrently inducing apoptosis and modulating autophagy.
- These findings suggest amantadine as a promising therapeutic candidate for glioma treatment.
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