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Autophagic cell death induced by resveratrol depends on the Ca(2+)/AMPK/mTOR pathway in A549 cells

Jun Zhang1, JenFu Chiu, Hongwei Zhang

  • 1Open Laboratory for Tumor Molecular Biology/Department of Biochemistry, Shantou University Medical College, Shantou, China.

Biochemical Pharmacology
|May 18, 2013
PubMed

Insights

Resveratrol induces lung cancer cell death through autophagy. This process involves calcium signaling and the AMPK-mTOR pathway, offering potential therapeutic insights.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • Resveratrol exhibits diverse biological activities, including anti-tumor effects.
  • The precise mechanism of resveratrol's anti-tumor action, particularly its induction of autophagy, remains unclear.

Purpose of the Study:

  • To investigate the role of autophagy in resveratrol-induced cell death in A549 human lung adenocarcinoma cells.
  • To elucidate the molecular mechanisms underlying resveratrol's autophagic cell death induction.

Main Methods:

  • Cell viability and death assays (MTT, clonogenic assays).
  • Autophagy assessment (monodansylcadaverine, transmission electron microscopy, LC3 expression).
  • Western blot analysis for cell signaling, Fura2-AM staining for intracellular calcium, and use of autophagy inhibitors and gene silencing.

Main Results:

  • Resveratrol induced significant A549 cell death mediated by autophagy.
  • Inhibition of autophagy (3-methyladenine) or knockdown of Atg5/Beclin-1 blocked resveratrol-induced cell death.
  • Resveratrol triggered intracellular calcium accumulation, activating AMPK and Raptor, while inhibiting p70S6K.

Conclusions:

  • Resveratrol-induced A549 cell death is mediated by autophagic cell death.
  • The Ca(2+)/AMPK-mTOR signaling pathway is crucial for resveratrol's autophagic cell death induction in lung cancer cells.

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