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Panduratin A induces protective autophagy in melanoma via the AMPK and mTOR pathway

Siew-Li Lai1, Mohd Rais Mustafa2, Pooi-Fong Wong1

  • 1Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia.

Phytomedicine : International Journal of Phytotherapy and Phytopharmacology
|April 16, 2018
PubMed
Abstract

Insights

Panduratin A induces autophagy in melanoma cells, which protects them from cell death. Inhibiting this autophagy enhances Panduratin A's cancer-killing effects by targeting mTOR and AMPK pathways.

Area of Science:

  • Cancer Biology
  • Molecular Oncology
  • Cellular Stress Responses

Background:

  • Autophagy modulation is a key strategy in cancer therapeutics, impacting drug resistance.
  • Panduratin A (PA), a plant compound, induces apoptosis in melanoma via ER stress.
  • PA treatment upregulated the autophagy marker LC3B in melanoma cells.

Purpose of the Study:

  • To investigate the role of autophagy induced by Panduratin A in melanoma cells.
  • To elucidate the signaling pathways involved in PA-induced autophagy.
  • To determine if modulating autophagy affects PA's cytotoxicity.

Main Methods:

  • Transmission electron microscopy to visualize autophagic structures.
  • Immunofluorescence staining for LC3B and p62/SQSMT1.
  • Western blotting to assess levels of autophagy and apoptosis markers (LC3B II, p62, ATG12, Beclin 1, p-S6, p-AMPK, cleaved PARP).

Main Results:

  • PA treatment led to the formation of autophagosomes and autolysosomes in A375 melanoma cells.
  • PA-induced autophagy involved mTOR inhibition and AMPK activation.
  • Autophagy inhibition enhanced PA-induced apoptosis, indicating a cytoprotective role for PA-induced autophagy.

Conclusions:

  • PA-induced autophagy in melanoma cells acts as a survival mechanism.
  • Targeting autophagy, specifically inhibiting mTOR and AMPK, can potentiate PA's anti-melanoma effects.
  • This suggests a potential therapeutic strategy combining PA with autophagy inhibitors.
Keywords:
AMPKAutophagyPanduratin AmTOR

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