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Updated: Aug 7, 2025

Isolation and Functional Assessment of Human Breast Cancer Stem Cells from Cell and Tissue Samples
07:03

Isolation and Functional Assessment of Human Breast Cancer Stem Cells from Cell and Tissue Samples

Published on: October 2, 2020

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A small molecule inhibitor of Notch1 modulates stemness and suppresses breast cancer cell growth

Uttara Saran1, Balaji Chandrasekaran1, Ashish Tyagi1

  • 1Texas A&M University, College Station, TX, United States.

Frontiers in Pharmacology
|March 13, 2023
PubMed

Insights

A novel small molecule, ASR490, effectively targets Notch1 signaling in breast cancer stem cells (BCSCs). This inhibition halts cancer growth and formation, offering a promising, non-toxic therapeutic strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • Breast cancer stem cells (BCSCs) are crucial for tumor growth and recurrence.
  • Notch1 signaling is a key pathway regulating BCSCs proliferation, survival, and differentiation.
  • Targeting BCSCs remains a clinical challenge.

Purpose of the Study:

  • To evaluate the efficacy of ASR490, a novel small molecule inhibitor, against BCSCs.
  • To investigate the mechanism of action of ASR490 in inhibiting Notch1 signaling.
  • To assess the therapeutic potential of ASR490 in preclinical breast cancer models.

Main Methods:

  • In vitro assays to assess BCSC inhibition, colony formation, and mammosphere formation.
  • Western blotting to analyze Notch1 intracellular domain (NICD) and downstream targets (Hey1, HES1).
  • In vivo xenograft models to evaluate tumor growth inhibition.
  • Assessment of autophagy-related protein expression and autophagosome-autolysosome fusion.

Main Results:

  • ASR490 significantly inhibited BCSCs (ALDH+, CD44+/CD24-) and breast cancer growth at nanomolar concentrations.
  • ASR490 downregulated NICD, Hey1, and HES1, indicating effective Notch1 pathway inhibition.
  • ASR490 induced autophagy-mediated growth inhibition in BCSCs.
  • ASR490 demonstrated a favorable safety profile, being non-toxic to healthy cells.
  • Oral administration of ASR490 suppressed BCSC and breast cancer tumor growth in vivo.

Conclusions:

  • ASR490 is a potent inhibitor of Notch1 signaling in BCSCs and breast cancer cells.
  • ASR490 exhibits therapeutic potential as a novel agent for breast cancer treatment.
  • ASR490 offers a targeted and non-toxic approach to eradicate breast cancer stem cells.
Keywords:
ASR490NOTCH1autophagybreast cancerbreast cancer stem cell (BCSC)

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