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Dihydrotanshinone-Induced NOX5 Activation Inhibits Breast Cancer Stem Cell through the ROS/Stat3 Signaling Pathway

Su-Lim Kim1, Hack Sun Choi1,2,3, Ji-Hyang Kim1

  • 1Department of Biotechnology, College of Applied Life Science, Jeju National University, Jeju, Republic of Korea.

Oxidative Medicine and Cellular Longevity
|April 26, 2019
PubMed

Insights

Dihydrotanshinone (DHTS) effectively inhibits cancer stem cell (CSC) formation and breast tumor growth. DHTS targets the ROS/Stat3/IL-6 pathway, offering a potential therapeutic strategy against CSCs.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Cancer stem cells (CSCs) drive tumor metastasis and recurrence, representing critical therapeutic targets.
  • Identifying novel agents that selectively target CSCs is crucial for improving cancer treatment outcomes.

Purpose of the Study:

  • To investigate the efficacy of dihydrotanshinone (DHTS) in inhibiting cancer stem cell formation and identify its underlying molecular mechanisms.
  • To evaluate DHTS as a potential therapeutic agent against breast CSCs.

Main Methods:

  • Assessed DHTS effects on mammosphere formation and xenograft tumor growth.
  • Quantified CSC populations (CD44high/CD24low, ALDH-expressing) and self-renewal genes (Nanog, SOX2, OCT4, C-Myc, CD44).
  • Investigated DHTS-induced NOX5 activation, calcium influx, reactive oxygen species (ROS) production, Stat3 phosphorylation, and IL-6 secretion.

Main Results:

  • DHTS demonstrated dose-dependent inhibition of mammosphere formation and significant tumor growth reduction in vivo.
  • DHTS decreased CSC populations and downregulated key self-renewal genes.
  • DHTS activated NOX5, leading to increased ROS production, which subsequently reduced Stat3 phosphorylation and IL-6 secretion, thereby disrupting the CSC self-renewal pathway.

Conclusions:

  • DHTS inhibits CSC formation by inducing ROS production via NOX5 activation, leading to the deregulation of the Stat3/IL-6 signaling pathway.
  • These findings highlight DHTS as a promising therapeutic agent for targeting breast CSCs and overcoming treatment resistance.

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