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Artemisia argyi extracts overcome lapatinib resistance via enhancing TMPRSS2 activation in HER2-positive breast

Chien-Yi Ho1,2,3, Cheng-Yen Wei4,5, Ruo-Wen Zhao4,5

  • 1Department of Biomedical Imaging and Radiological Science, China Medical University, Taichung, Taiwan.

Environmental Toxicology
|March 6, 2024
PubMed

Insights

Artemisia argyi compounds inhibit lapatinib-resistant HER2-positive breast cancer growth by enhancing transmembrane serine protease 2 (TMPRSS2) activity. This suggests TMPRSS2 as a key factor in lapatinib sensitivity and Artemisia argyi as a potential therapy to overcome resistance.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Breast cancer is a leading global cause of cancer mortality in women.
  • HER2 overexpression in 25% of breast cancers leads to aggressive phenotypes and poor prognoses.
  • Acquired resistance to HER2 tyrosine kinase inhibitors (HER2 TKIs) like Lapatinib is a major challenge in metastatic breast cancer treatment.

Purpose of the Study:

  • To investigate the potential of Artemisia argyi, a Chinese herbal medicine, in overcoming HER2 TKI resistance in breast cancer.
  • To explore the role of transmembrane serine protease 2 (TMPRSS2) in lapatinib sensitivity and resistance.

Main Methods:

  • Analysis of The Cancer Genome Atlas (TCGA) data to correlate TMPRSS2 expression with breast cancer outcomes and lapatinib response.
  • In vitro studies using compounds from Artemisia argyi (eriodictyol, umbelliferone) against lapatinib-resistant HER2-positive breast cancer cells.
  • Mechanistic investigation of how Artemisia argyi compounds affect HER2 kinase activation and TMPRSS2 activity.

Main Results:

  • Diminished TMPRSS2 expression was observed in breast cancer patients, correlating with unfavorable outcomes.
  • Higher TMPRSS2 expression was associated with lapatinib responsiveness.
  • Eriodictyol and umbelliferone from Artemisia argyi inhibited the growth of lapatinib-resistant HER2-positive breast cancer cells.
  • These compounds suppressed HER2 kinase activation by enhancing TMPRSS2 activity.

Conclusions:

  • TMPRSS2 is a critical determinant of lapatinib sensitivity in HER2-positive breast cancer.
  • Artemisia argyi compounds show potential in overcoming lapatinib resistance by activating TMPRSS2.
  • This study provides a foundation for developing novel therapeutic strategies to improve treatment outcomes for HER2-positive breast cancer.
Keywords:
Artemisia argyiHER2TMPRSS2breast cancereriodictyolumbelliferone

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