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Tanshinone IIA inhibits gastric cancer cell stemness through inducing ferroptosis

Haiwei Ni1, Guojing Ruan1, Cheng Sun2

  • 1School of Life Science and Technology, Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing, China.

Environmental Toxicology
|October 18, 2021
PubMed

Insights

Tanshinone IIA, derived from Salvia Miltiorrhza, reduces gastric cancer cell stemness. This effect is partly achieved by inducing ferroptosis, a form of cell death, in cancer cells.

Area of Science:

  • Oncology
  • Pharmacology
  • Cell Biology

Background:

  • Tanshinone IIA, an active compound from Salvia Miltiorrhza, is known to inhibit tumor growth and metastasis.
  • The impact of Tanshinone IIA on gastric cancer cell stemness remains largely unexplored.
  • Gastric cancer stem cells contribute to tumor recurrence and metastasis.

Purpose of the Study:

  • To investigate the effect of Tanshinone IIA on gastric cancer cell stemness.
  • To elucidate the underlying mechanism, particularly the role of ferroptosis.

Main Methods:

  • Gastric cancer cell lines were treated with Tanshinone IIA.
  • Cell stemness was assessed via spheroid formation assays, flow cytometry, and analysis of stemness markers (OCT3/4, ALDH1A1, CD44).
  • Lipid peroxidation and glutathione levels were measured to assess ferroptosis. Ferroptosis inducers and inhibitors were used to confirm the mechanism.

Main Results:

  • Tanshinone IIA significantly reduced gastric cancer cell stemness, indicated by decreased spheroid formation and altered expression of stemness markers.
  • Tanshinone IIA treatment led to increased lipid peroxidation and decreased glutathione levels, suggesting ferroptosis induction.
  • Ferroptosis inducers mimicked the stemness-inhibiting effect of Tanshinone IIA.
  • Inhibition of ferroptosis (using Fer-1 or SLC7A11 overexpression) reversed the anti-stemness effects of Tanshinone IIA.

Conclusions:

  • Tanshinone IIA effectively inhibits gastric cancer cell stemness.
  • The mechanism involves the induction of ferroptosis in gastric cancer cells.
  • Targeting ferroptosis presents a potential therapeutic strategy against gastric cancer stem cells.
Keywords:
SLC7A11Tanshinone IIAferroptosisgastric cancerstemness

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