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Celastrol increases anoikis sensitivity to suppress triple-negative breast cancer via EGFR pathway and p-EMT state

Jue Yang1, Xiangpeng Wang1, Xiuyun Bai1

  • 1School of Materia Medica, Beijing University of Chinese Medicine, Beijing, China.

Frontiers in Pharmacology
|March 18, 2026
PubMed

Insights

Celastrol effectively inhibits the proliferation, invasion, and migration of metastatic triple-negative breast cancer (TNBC) cells. This natural compound shows promise as a new therapeutic agent for TNBC by suppressing epithelial-mesenchymal transition (EMT) and anoikis resistance.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Metastatic triple-negative breast cancer (TNBC) poses a significant clinical challenge due to limited treatment options.
  • Celastrol (Cel), a natural compound, exhibits anti-neoplastic properties.
  • There is a need for novel anti-metastatic drugs for TNBC.

Purpose of the Study:

  • To investigate the anti-metastatic effects of Celastrol on anoikis-resistant TNBC cells (TNBC-AR).
  • To explore the underlying molecular mechanisms of Celastrol's action against TNBC metastasis.

Main Methods:

  • Cell proliferation was assessed using CCK-8 and colony formation assays.
  • Cell invasion and migration were evaluated by wound healing and Transwell assays.
  • Molecular mechanisms were explored through bioinformatics analysis, Western blotting, and intervention experiments, focusing on epithelial-mesenchymal transition (EMT) and the EGFR/MEK/ERK pathway.

Main Results:

  • Celastrol inhibited the proliferation of MDA-MB-231-AR and BT-549-AR cells (IC50 values ~1.5-1.7 μM).
  • Celastrol significantly suppressed the invasion, migration, cluster formation, and enhanced anoikis in TNBC-AR cells.
  • Celastrol treatment reduced the p-EMT state and EGFR/MEK/ERK pathway activation in TNBC-AR cells.

Conclusions:

  • Celastrol demonstrates potent anti-metastatic activity against anoikis-resistant TNBC cells.
  • Celastrol's mechanism involves suppressing EMT and inhibiting the EGFR/MEK/ERK signaling pathway.
  • Celastrol is a potential therapeutic candidate for treating metastatic TNBC.
Keywords:
anoikiscelastrolcirculating tumor cellstriple-negative breast cancertumor metastasis

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