HTB50-2 Inhibits Growth and Migration of Triple-negative Breast Cancer via FOSL2/FOXC1 Signaling Axis and Subsequent

Na Liu1, Wen-Ying Yin1, Wen-Qi Duan1

  • 1School of Biological Science and Technology, University of Jinan, Jinan, 250022, China.

PubMed
Abstract

Insights

14β-hydroxy-3β-(β-D-Glucopyranosyloxy)-5α-bufa-20,22-dienolide (HTB50-2) induces ferroptosis in Triple-Negative Breast Cancer (TNBC) cells, inhibiting tumor growth. This natural compound targets the FOSL2/FOXC1 signaling pathway for potential TNBC therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Ferroptosis induction is a promising cancer therapy strategy.
  • Natural products are gaining interest for cancer treatment.
  • Triple-Negative Breast Cancer (TNBC) remains a therapeutic challenge.

Purpose of the Study:

  • To evaluate the anticancer efficacy of HTB50-2 in TNBC.
  • To elucidate the underlying mechanisms of HTB50-2's action.
  • To explore the role of FOSL2 and FOXC1 in HTB50-2-mediated ferroptosis.

Main Methods:

  • Sulforhodamine B assay and cell migration assays (wound healing, transwell).
  • In vivo studies using orthotopic transplantation in BALB/c mice.
  • Transcriptome sequencing, Western blot, and immunohistochemistry to analyze FOSL2 and FOXC1.

Main Results:

  • HTB50-2 effectively induced ferroptosis in TNBC cells.
  • HTB50-2 inhibited tumor growth in vivo by promoting ferroptosis.
  • FOSL2 was identified as a key mediator of HTB50-2-induced ferroptosis, regulating FOXC1.

Conclusions:

  • HTB50-2 exhibits anti-cancer properties in TNBC through ferroptosis induction.
  • The FOSL2/FOXC1 signaling pathway is crucial for HTB50-2's therapeutic effect.
  • HTB50-2 demonstrates significant potential for TNBC treatment.

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