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Avicularin induces apoptosis in NSCLC by promoting USP7-mediated degradation of FOXM1

Jiangyue Du1, Kuai Yu2, Jian Zeng3

  • 1Department of General Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Zhejiang, China.

Naunyn-Schmiedeberg'S Archives of Pharmacology
|August 11, 2025
PubMed

Insights

Avicularin (Avi) effectively targets non-small cell lung cancer (NSCLC) by degrading the FOXM1 protein, offering a potential new treatment. This natural compound shows promise as a standalone therapy or in combination with existing treatments.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Non-small cell lung cancer (NSCLC) is a major global health concern, necessitating innovative therapeutic approaches.
  • Avicularin (Avi), a flavonoid, demonstrates anti-cancer properties by reducing NSCLC cell viability and inducing apoptosis with low toxicity to normal cells.

Purpose of the Study:

  • To elucidate the mechanism of Avicularin's anti-NSCLC effects.
  • To evaluate Avicularin's therapeutic potential as a monotherapy and in combination with gefitinib.

Main Methods:

  • Investigated Avicularin's impact on FOXM1 protein and mRNA levels in NSCLC cells.
  • Assessed the role of ubiquitination and USP7 in Avicularin's mechanism of action.
  • Evaluated Avicularin's efficacy and toxicity in vivo using A549 xenograft models.
  • Examined the combined effects of Avicularin and gefitinib in NSCLC treatment.

Main Results:

  • Avicularin selectively reduced FOXM1 protein expression via post-transcriptional regulation, promoting its polyubiquitination and degradation by USP7.
  • Overexpression of FOXM1 or USP7 counteracted Avicularin's cytotoxic effects.
  • Avicularin inhibited tumor growth in vivo without systemic toxicity and enhanced gefitinib's anti-cancer activity.

Conclusions:

  • Avicularin exhibits potent anti-NSCLC activity by promoting USP7-dependent degradation of FOXM1.
  • Avicularin holds potential as a novel monotherapy or adjuvant treatment for NSCLC, particularly in combination with EGFR-targeted therapies.
Keywords:
ApoptosisAvicularinFOXM1Non-small cell lung cancerUSP7

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