Celastrol and Triptolide Suppress Stemness in Triple Negative Breast Cancer: Notch as a Therapeutic Target for Stem

Prabhu Ramamoorthy1, Prasad Dandawate1, Roy A Jensen2

  • 1Department of Cancer Biology, University of Kansas Medical Center, Kansas City, KS 66160, USA.

Biomedicines
|April 30, 2021
PubMed

Insights

Celastrol and triptolide inhibit cancer stemness in triple-negative breast cancer (TNBC). These natural compounds target cancer stem cells and Notch signaling, offering a potential strategy to reduce TNBC progression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Natural Products Chemistry

Background:

  • Triple-negative breast cancer (TNBC) accounts for ~15% of breast cancers, characterized by poor survival and high metastatic potential.
  • Cancer stem cells (CSCs) within TNBC tumors drive tumorigenesis and metastasis.
  • Notch signaling is crucial for stem cell renewal and is implicated in cancer progression.

Purpose of the Study:

  • To investigate the efficacy of natural compounds celastrol and triptolide in inhibiting stemness in TNBC.
  • To elucidate the role of Notch signaling in TNBC stemness and the effect of these compounds on the pathway.

Main Methods:

  • Utilized TNBC cell lines (MDA-MB-231, BT20) and patient-derived primary cells (PD-TNBC).
  • Assessed stemness using the mammosphere assay.
  • Quantified expression of CSC markers (DCLK1, ALDH1, CD133) and Notch signaling components (Notch-1, NICD, HES-1, HEY-1).
  • Investigated the effect of ectopic Notch intracellular domain 1 (NICD1) overexpression.

Main Results:

  • Celastrol and triptolide significantly suppressed mammosphere formation in TNBC cells.
  • Both compounds reduced the expression of key CSC markers (DCLK1, ALDH1, CD133).
  • Celastrol and triptolide inhibited Notch-1 activation and downstream targets (HES-1, HEY-1).
  • Ectopic overexpression of NICD1 partially rescued cell proliferation and mammosphere formation, confirming Notch pathway involvement.

Conclusions:

  • Celastrol and triptolide effectively inhibit stemness in triple-negative breast cancer.
  • Targeting cancer stem cells and the Notch signaling pathway represents a promising therapeutic strategy for TNBC.
  • These findings highlight the potential of natural compounds in combating TNBC progression.

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