Daurisoline suppress glioma progression by inhibiting autophagy through PI3K/AKT/mTOR pathway and increases TMZ

Hai-Tang Yin1, Hui-Lu1, Ji-Hong Yang1

  • 1Department of Pharmacy, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou Province, PR China; College of Pharmacy, Guizhou Medical University, Guiyang, Guizhou Province, PR China.

PubMed

Insights

Daurisoline (DAS) shows potent anti-glioma effects by inducing apoptosis and cell cycle arrest. It also enhances temozolomide (TMZ) efficacy by inhibiting autophagy, offering a new strategy for chemoresistant glioma.

Area of Science:

  • Neuro-oncology
  • Cancer Biology
  • Pharmacology

Background:

  • Glioma is a common primary malignant brain tumor.
  • Temozolomide (TMZ) is a standard chemotherapy with limited efficacy due to resistance.
  • Novel therapeutic agents are needed for effective glioma treatment.

Purpose of the Study:

  • To investigate the anti-glioma effects of Daurisoline (DAS).
  • To explore DAS's mechanism of action in glioma cells.
  • To evaluate DAS's potential to overcome temozolomide resistance.

Main Methods:

  • Cytotoxicity screening of 30 compounds using CCK-8 assay.
  • Assessment of apoptosis, cell cycle, migration, and invasion.
  • Analysis of the PI3K/AKT/mTOR pathway and autophagy.
  • In vivo efficacy study using a nude mice xenograft model.

Main Results:

  • Daurisoline (DAS) demonstrated potent cytotoxicity against glioma cells.
  • DAS induced apoptosis via caspase activation and G1 cell cycle arrest.
  • DAS suppressed glioma cell migration and invasion by regulating epithelial-mesenchymal transition.
  • DAS impaired late-stage autophagic flux through the PI3K/AKT/mTOR pathway.
  • DAS inhibited TMZ-induced autophagy, enhancing TMZ chemosensitivity.
  • In vivo studies confirmed DAS restrains glioma proliferation and improves TMZ chemosensitivity.

Conclusions:

  • Daurisoline (DAS) exhibits significant anti-glioma activity.
  • DAS enhances the efficacy of temozolomide (TMZ) in chemoresistant glioma models.
  • DAS represents a promising therapeutic candidate for glioma treatment.

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