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PERK/eIF-2α/CHOP Pathway Dependent ROS Generation Mediates Butein-induced Non-small-cell Lung Cancer Apoptosis and

Shouyin Di1, Chongxi Fan2, Zhiqiang Ma1

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

International Journal of Biological Sciences
|July 31, 2019
PubMed

Insights

Butein effectively combats non-small cell lung cancer (NSCLC) by inducing apoptosis via endoplasmic reticulum (ER) stress and reactive oxygen species (ROS) generation. This study highlights butein as a potential therapeutic agent for NSCLC treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Butein, a chalcone, shows anticancer properties but its mechanism against non-small cell lung cancer (NSCLC) is unclear.
  • Understanding butein's anti-NSCLC effects is crucial for developing novel cancer therapies.

Purpose of the Study:

  • To investigate the anti-NSCLC effects of butein.
  • To elucidate the underlying molecular mechanisms, focusing on endoplasmic reticulum (ER) stress and reactive oxygen species (ROS) generation.

Main Methods:

  • Treated NSCLC cell lines and PC-9 xenografts with butein.
  • Assessed cell viability, adhesion, migration, invasion, colony formation, apoptosis, and cell cycle.
  • Utilized 4-phenylbutyric acid (4-PBA), CHOP siRNA, N-acetyl-L-cysteine (NAC), and Z-VAD-FMK (z-VAD) to investigate mechanisms.
  • Measured ER stress and ROS generation both in vitro and in vivo.

Main Results:

  • Butein significantly reduced NSCLC cell viability, migration, invasion, and colony formation, while inducing apoptosis and G2/M phase arrest.
  • Butein inhibited PC-9 xenograft growth in vivo.
  • The anti-NSCLC effects were mediated by activating ER stress-dependent ROS generation, which was reversed by inhibiting ER stress or oxidative stress.

Conclusions:

  • Butein exhibits potent anti-NSCLC activity through ER stress-dependent ROS generation and apoptosis induction.
  • Butein is a promising therapeutic candidate for NSCLC treatment.
Keywords:
ApoptosisButeinEndoplasmic reticulum stressNon-small-cell lung cancerOxidative stress

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