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Bacterial Cyclodipeptides Inhibit Invasiveness and Metastasis Progression in the Triple-Negative Breast Cancer

Mayra Xochitl Durán-Maldonado1, Ximena Hernández-Ramos1, Marlene Estefania Campos-Morales1

  • 1Instituto de Investigaciones Químico Biológicas, Universidad Michoacana de San Nicolás de Hidalgo, Morelia 58030, Michoacan, Mexico.

Molecules (Basel, Switzerland)
|February 13, 2026
PubMed

Insights

Bacterial cyclodipeptides (CDPs) show potent anti-metastatic effects against triple-negative breast cancer (TNBC) by inhibiting key signaling pathways. CDPs significantly suppressed tumor growth and metastasis in preclinical models, outperforming methotrexate.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Triple-negative breast cancer (TNBC) is an aggressive subtype with poor prognosis and high metastatic potential.
  • Bacterial cyclodipeptides (CDPs) exhibit anticancer properties through various signaling pathways.
  • Targeting metastasis is crucial for improving survival rates in TNBC patients.

Purpose of the Study:

  • To evaluate the anti-metastatic efficacy of bacterial cyclodipeptides (CDPs) in triple-negative breast cancer (TNBC) models.
  • To investigate the molecular mechanisms underlying the anti-metastatic effects of CDPs.
  • To compare the efficacy of CDPs with methotrexate (MTX) in TNBC treatment.

Main Methods:

  • In vitro studies using MDA-MB-231 cell line to assess migration and invasion.
  • In vivo studies using an advanced-stage TNBC xenograft mouse model.
  • Analysis of key signaling proteins (e.g., p-Akt, p-Gab1, FOXO1) and gene expression (e.g., EMT, immune modulation genes).

Main Results:

  • CDPs significantly reduced MDA-MB-231 cell migration and invasion, surpassing MTX.
  • CDPs inhibited Akt/mTOR/S6K phosphorylation and downstream targets.
  • Combined CDP and MTX treatment showed synergistic tumor suppression and near-complete elimination of primary tumors and metastases in mice.
  • CDP treatment modulated EMT, invasiveness, and immune-related gene expression, restoring normal levels more effectively than MTX.

Conclusions:

  • CDPs possess significant anti-metastatic potential against TNBC.
  • The anti-metastatic effects of CDPs involve the modulation of the Akt/mTOR/S6K pathway, epithelial-mesenchymal transition (EMT), invasiveness, and immune responses.
  • CDPs demonstrate promise for further preclinical development as an anti-TNBC metastasis therapy.
Keywords:
anti-metastaticcyclodipeptidestriple-negative breast cancer

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