Corynoxine triggers cell death via activating PP2A and regulating AKT-mTOR/GSK3β axes in NSCLC

Guoqing Hou1, Weihua Hu2, Yazhou Sang3

  • 1School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China; School of Medicine, Taizhou University, Taizhou 318000, Zhejiang, China.

PubMed

Insights

Corynoxine (Cory), a natural compound, effectively inhibits non-small cell lung cancer (NSCLC) growth. It triggers apoptosis and autophagy by modulating key signaling pathways, offering a promising new therapeutic avenue for NSCLC treatment.

Area of Science:

  • Pharmacology
  • Oncology
  • Molecular Biology

Background:

  • Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality worldwide.
  • There is a continuous need for novel therapeutic agents with improved efficacy and reduced toxicity.
  • Natural products, such as Corynoxine (Cory) from Uncaria rhynchophylla, represent a potential source for anticancer drug discovery.

Purpose of the Study:

  • To investigate the anticancer activity of Corynoxine (Cory) in non-small cell lung cancer (NSCLC).
  • To elucidate the pharmacological mechanisms underlying Cory's effects on NSCLC cells.
  • To evaluate Cory's potential as a lead compound for NSCLC drug development.

Main Methods:

  • Cell proliferation and viability assays (MTT, colony formation).
  • Flow cytometry for apoptosis, cell cycle, and mitochondrial membrane potential analysis.
  • Microscopy (fluorescence, electron) for autophagy detection.
  • Western blotting, gene manipulation, co-immunoprecipitation, and bioinformatics for pathway analysis.

Main Results:

  • Cory inhibits NSCLC cell proliferation both in vitro and in vivo.
  • Cory enhances protein phosphatase 2A (PP2A) activity, leading to AKT inhibition.
  • Cory triggers autophagy via the AKT/mTOR pathway and induces apoptosis via the AKT/GSK3β pathway.
  • In vivo studies confirm Cory's therapeutic efficacy in NSCLC models.

Conclusions:

  • Corynoxine exhibits significant anticancer activity against NSCLC.
  • Cory's mechanism involves PP2A activation, modulating AKT signaling to induce apoptosis and autophagy.
  • Cory holds promise as a potential lead compound for developing novel NSCLC therapies.

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