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Eriocalyxin B induces ferroptosis through SIRT3 inhibition in triple-negative breast cancer

  • 0Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs, School of Life Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China; School of Pharmaceutical Sciences, Health Science Center, Shenzhen University, Shenzhen 518000, China; Key Laboratory of Advanced Technologies of Material, Minister of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, Sichuan, China.
Phytomedicine : International Journal of Phytotherapy and Phytopharmacology +

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September 21, 2025

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September 21, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

Eriocalyxin B (Eri B) induces ferroptosis in triple-negative breast cancer (TNBC) by inhibiting sirtuin 3 (SIRT3) via STAT3 targeting. This natural compound shows significant antitumor activity, offering a potential new therapy for TNBC.

Area Of Science

  • Oncology
  • Molecular Biology
  • Biochemistry

Background

  • Triple-negative breast cancer (TNBC) is aggressive with limited treatment options.
  • TNBC's metabolic vulnerabilities, including high iron and lipid levels, make it susceptible to ferroptosis.
  • Eriocalyxin B (Eri B), a natural diterpenoid, possesses anticancer properties needing further exploration.

Purpose Of The Study

  • To investigate the therapeutic mechanism of Eri B-induced ferroptosis in TNBC.
  • To determine if Eri B targets STAT3 and impacts the SIRT3 pathway.
  • To evaluate the in vitro and in vivo efficacy of Eri B against TNBC.

Main Methods

  • Cell proliferation and metastasis assays (colony formation, wound healing, transwell).
  • RNA sequencing (RNA-seq), flow cytometry, electron microscopy, and western blotting to confirm ferroptosis.
  • Molecular docking, SPR, and CETSA to validate Eri B-STAT3 interaction.
  • In vivo xenograft models to assess anti-TNBC activity.

Main Results

  • Eri B demonstrated significant in vitro and in vivo antitumor activity by inducing ferroptosis.
  • RNA-seq revealed Eri B inhibits sirtuin 3 (SIRT3), impacting the NRF2-GPX4 pathway and causing oxidative stress.
  • Eri B directly targets STAT3, suppressing SIRT3 transcription and regulating fatty acid metabolism and redox homeostasis.

Conclusions

  • Eri B is a novel ferroptosis inducer for TNBC treatment.
  • Inhibition of SIRT3 by Eri B presents a promising therapeutic strategy for TNBC.
  • Targeting STAT3-SIRT3 axis offers a new avenue for TNBC drug development.

Keywords: