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Related Experiment Video

Updated: Nov 7, 2025

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KEAP1 Is Required for Artesunate Anticancer Activity in Non-Small-Cell Lung Cancer.

Kristen S Hill1, Anthony McDowell2, J Robert McCorkle1

  • 1Markey Cancer Center, University of Kentucky, Lexington, KY 40536, USA.

Cancers
|April 30, 2021
PubMed
Summary

Artesunate

Keywords:
KEAP1NRF2NSCLCartesunate

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Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Artesunate, a malaria treatment, exhibits anticancer properties via reactive oxygen species induction.
  • The KEAP1/NRF2 pathway regulates oxidative stress and is frequently mutated in non-small-cell lung cancer (NSCLC).

Purpose of the Study:

  • To investigate the role of KEAP1 in artesunate sensitivity in NSCLC.
  • To explore the therapeutic potential of targeting the KEAP1/NRF2 pathway in NSCLC.

Main Methods:

  • Dose-response assays were performed on NSCLC cell lines with varying KEAP1/NRF2 pathway status.
  • KEAP1 was silenced using siRNA, and NRF2 was inhibited pharmacologically using ML385.

Main Results:

  • NSCLC cells with inactivating KEAP1 mutations (A549) showed resistance to artesunate.
  • KEAP1 knockdown increased artesunate resistance, while NRF2 inhibition partially restored sensitivity in resistant cells.
  • Artesunate and NRF2 inhibitor ML385 showed synergistic effects in both sensitive and resistant NSCLC cells.

Conclusions:

  • KEAP1 is essential for artesunate's anticancer activity in NSCLC.
  • Targeting NRF2 with inhibitors may be a viable strategy for treating NSCLC patients with KEAP1/NRF2 pathway mutations.