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Resveratrol induces autophagy-dependent apoptosis in HL-60 cells

Yingying Fan1, Jen-Fu Chiu1, Jing Liu2

  • 1Open Laboratory for Tumor Molecular Biology/Department of Biochemistry/The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Xinling Road 22, Shantou, China.

BMC Cancer
|May 24, 2018
PubMed
Abstract

Insights

Resveratrol induces apoptosis in cancer cells by activating autophagy through the LKB1-AMPK-mTOR pathway. Inhibiting autophagy reduces resveratrol-induced apoptosis, suggesting a crucial role for autophagy in this process.

Area of Science:

  • Cell Biology
  • Molecular Oncology
  • Biochemistry

Background:

  • Resveratrol (RSV) is known to induce apoptosis via cell cycle arrest and mitochondrial changes.
  • The relationship between RSV-induced apoptosis and autophagy remains largely unexplored.

Purpose of the Study:

  • To investigate the interplay between resveratrol-induced apoptosis and autophagy.
  • To elucidate the signaling pathways involved in this interaction.

Main Methods:

  • Western blotting and immunofluorescence to detect apoptosis and autophagy markers.
  • Flow cytometry to assess mitochondrial membrane potential.
  • Pharmacological (3-methyladenine) and genetic (siRNA) inhibition of autophagy.

Main Results:

  • Resveratrol triggers apoptosis through intrinsic and extrinsic pathways, evidenced by altered Bax/Bcl-2 ratio and caspase activation.
  • Resveratrol enhances autophagy, indicated by increased LC3-II levels and autophagosome formation, dependent on the LKB1-AMPK-mTOR pathway.
  • Inhibition of autophagy significantly attenuates resveratrol-induced apoptosis markers.

Conclusions:

  • Resveratrol-induced apoptosis in HL-60 cells is critically dependent on autophagy.
  • Autophagy activation occurs via LKB1-AMPK and PI3K/AKT-regulated mTOR signaling pathways.
Keywords:
AMPK-mTORApoptosisAutophagyCell deathHL-60PI3K-AktResveratrol

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