Related Experiment Video

Updated: Jun 28, 2025

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
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Thiostrepton suppresses triple-negative breast cancer through downregulating c-FLIP/SMAD2/3 signaling pathway

Wen-Die Wang1, Chao-Yang Zeng1, Yue Shang1

  • 1Department of Cancer Research, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Beijing 100050, China.

Journal of Asian Natural Products Research
|April 18, 2024
PubMed

Insights

Thiostrepton combats triple-negative breast cancer (TNBC) by targeting the c-FLIP/SMAD2/3 pathway. This study uncovers a novel molecular mechanism for thiostrepton

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Triple-negative breast cancer (TNBC) is an aggressive subtype with limited treatment options and poor prognosis.
  • Thiostrepton, a natural compound, has demonstrated anti-tumor effects in various cancers, including TNBC.

Purpose of the Study:

  • To elucidate the novel molecular mechanisms underlying thiostrepton's anti-tumor activity in TNBC.
  • To investigate the role of the c-FLIP/SMAD2/3 signaling pathway in thiostrepton's efficacy.

Main Methods:

  • Utilized MDA-MB-231 TNBC cell line.
  • Assessed cell viability, c-FLIP expression, and SMAD2/3 phosphorylation.
  • Employed gene overexpression (c-FLIP) and knockdown (SMAD2/3) techniques.

Main Results:

  • Thiostrepton inhibited MDA-MB-231 cell viability, decreasing c-FLIP and p-SMAD2/3 levels.
  • Overexpression of c-FLIP reduced thiostrepton sensitivity, while SMAD2/3 knockdown enhanced it.
  • Modulation of c-FLIP affected SMAD2/3 expression and phosphorylation, and vice versa.

Conclusions:

  • The study identifies the c-FLIP/SMAD2/3 signaling pathway as a novel mechanism for thiostrepton's anti-tumor effects in TNBC.
  • Findings suggest potential therapeutic strategies targeting this pathway for TNBC treatment.
Keywords:
SMAD2/3Thiostreptonc-FLIPtriple-negative breast cancer (TNBC)

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