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Salinomycin-induced autophagy blocks apoptosis via the ATG3/AKT/mTOR signaling axis in PC-3 cells

Yunsheng Zhang1, Fang Li2, Luogen Liu1

  • 1Clinical Research Institute, The Second Affiliated Hospital, University of South China, Hengyang 421001, PR China.

Life Sciences
|July 4, 2018
PubMed
Abstract

Insights

Salinomycin triggers autophagy, a process that blocks apoptosis in prostate cancer cells. This study reveals salinomycin-induced autophagy inhibits cancer cell death via the ATG3/AKT/mTOR pathway.

Area of Science:

  • Oncology
  • Cell Biology
  • Molecular Mechanisms

Background:

  • Prostate cancer remains a significant health concern, necessitating novel therapeutic strategies.
  • Salinomycin, a polyether ionophore, exhibits anti-cancer properties.
  • Autophagy plays a complex role in cancer, potentially promoting or inhibiting tumor progression.

Purpose of the Study:

  • To elucidate the mechanism by which salinomycin induces autophagy and blocks apoptosis in PC-3 prostate cancer cells.
  • To investigate the role of autophagy regulation in salinomycin's anti-cancer effects.
  • To identify key molecular players in the salinomycin-induced autophagy-apoptosis interplay.

Main Methods:

  • Utilized flow cytometry, JC-1 staining, and western blotting to assess anti-cancer effects.
  • Evaluated autophagic flux using western blotting, GFP-LC3 puncta assays, immunofluorescence, and electron microscopy.
  • Employed lentivirus-mediated shRNA to silence ATG3, ATG5, and ATG7, key autophagy regulators.

Main Results:

  • Salinomycin effectively induced both apoptosis and autophagy in PC-3 cells.
  • Inhibition of autophagy potentiated salinomycin-induced apoptosis.
  • Downregulation of ATG3 was identified as crucial for salinomycin-induced autophagy to block apoptosis via the AKT/mTOR signaling axis.

Conclusions:

  • Salinomycin-induced autophagy inhibits apoptosis in PC-3 prostate cancer cells through the ATG3/AKT/mTOR signaling pathway.
  • This finding provides novel insights into the anti-cancer mechanisms of salinomycin.
  • Targeting the ATG3/AKT/mTOR axis may represent a therapeutic strategy for prostate cancer.
Keywords:
ATG3/AKT/mTOR signaling axisAutophagyPC-3 cellsSalinomycin

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