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Pterostilbene exerts anticancer activity on non-small-cell lung cancer via activating endoplasmic reticulum stress

Zhiqiang Ma1, Yang Yang2,3,4, Shouyin Di1

  • 1Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, 1 Xinsi Road, Xi'an, 710038, China.

Scientific Reports
|August 16, 2017
PubMed

Insights

Pterostilbene (PT) enhances endoplasmic reticulum stress (ERS) signaling, reducing non-small-cell lung cancer (NSCLC) cell viability and inducing apoptosis. This suggests ERS activation is a novel therapeutic mechanism for PT against lung cancer.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Pterostilbene (PT), a resveratrol analog, shows anticarcinogenic potential against non-small-cell lung cancer (NSCLC).
  • The precise molecular mechanisms underlying PT's anti-NSCLC effects are not fully understood.

Purpose of the Study:

  • To investigate the anti-NSCLC mechanisms of Pterostilbene (PT).
  • To determine if endoplasmic reticulum stress (ERS) signaling is involved in PT's anti-cancer activity.

Main Methods:

  • Treatment of human PC9 and A549 NSCLC cell lines with PT.
  • Analysis of ERS signaling pathway components (p-PERK, IRE1, ATF4, CHOP).
  • Assessment of cell viability, apoptosis, migration, adhesion, glutathione (GSH) levels, reactive oxygen species (ROS) generation, Caspase 3 activity, and mitochondrial membrane potential.
  • In vitro and in vivo studies using CHOP siRNA and thapsigargin.

Main Results:

  • PT treatment dose- and time-dependently enhanced ERS signaling, decreasing cell viability and inducing apoptosis in NSCLC cells.
  • PT reduced NSCLC cell migration and adhesion, downregulated GSH, increased ROS, and altered Caspase 3 activity and mitochondrial membrane potential.
  • ERS inhibition via CHOP siRNA reversed PT's effects, while ERS induction with thapsigargin enhanced them.
  • In vivo studies confirmed PT's anti-cancer activity via ERS and apoptosis modulation, enhanced by thapsigargin.

Conclusions:

  • Endoplasmic reticulum stress (ERS) activation is a key mechanism for Pterostilbene's (PT) anti-NSCLC effects.
  • PT's ability to induce ERS, apoptosis, and reduce cell viability offers a novel therapeutic strategy for lung cancer.
  • Targeting ERS signaling presents a promising avenue for developing new lung cancer interventions.

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