Amantadine against glioma via ROS-mediated apoptosis and autophagy arrest

Cell Death Dis. 2024 Nov 15;15(11):834. doi: 10.1038/s41419-024-07228-x.

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.

MeSH terms

  • Amantadine* / pharmacology
  • Animals
  • Apoptosis* / drug effects
  • Autophagy* / drug effects
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology
  • Cell Line, Tumor
  • Glioma* / drug therapy
  • Glioma* / metabolism
  • Glioma* / pathology
  • Humans
  • Lysosomes / drug effects
  • Lysosomes / metabolism
  • Mice
  • Mice, Nude
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Reactive Oxygen Species* / metabolism
  • Xenograft Model Antitumor Assays

Substances

  • Amantadine
  • Reactive Oxygen Species