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Scoparone induces both apoptosis and ferroptosis via multiple mechanisms in non-small-cell lung cancer cells

Hongping Shen1, Yiting Wei2, Qunying Yang3

  • 1Department of Chinese Medicine, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang Province, China.

Toxicology in Vitro : an International Journal Published in Association with BIBRA
|June 14, 2023
PubMed

Insights

Scoparone effectively inhibits non-small-cell lung cancer (NSCLC) cell growth and triggers cell death through apoptosis and ferroptosis. This natural compound shows promise as a novel therapeutic for NSCLC treatment.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Non-small-cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality worldwide.
  • Novel therapeutic strategies targeting cancer cell death pathways are urgently needed.
  • Scoparone (6,7-dimethoxycoumarin) is a natural compound with potential anti-cancer properties.

Purpose of the Study:

  • To investigate the anti-tumour effects of scoparone in NSCLC cells.
  • To elucidate the mechanisms underlying scoparone-induced cell death.
  • To evaluate scoparone as a potential therapeutic agent for NSCLC.

Main Methods:

  • Cell proliferation assays
  • Apoptosis and ferroptosis detection assays
  • Western blotting to assess protein levels and ubiquitination
  • Reactive oxygen species (ROS) measurement
  • Analysis of lipid peroxidation and iron levels

Main Results:

  • Scoparone significantly inhibited NSCLC cell proliferation and induced cell death.
  • Scoparone triggered both apoptosis and ferroptosis in NSCLC cells.
  • Mechanistically, scoparone led to FBW7-mediated ubiquitination and downregulation of Mcl-1, induced ROS-dependent Bax activation, and activated the ROS/JNK/SP1/ACSL4 axis to promote ferroptosis.

Conclusions:

  • Scoparone exhibits potent anti-tumour activity against NSCLC cells.
  • Scoparone induces cell death via both apoptosis and ferroptosis through distinct molecular pathways.
  • Scoparone represents a promising candidate for the development of novel NSCLC therapies.
Keywords:
ACSL4Cell deathMcl-1Non-small cell lung cancerScoparone

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