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Hinokitiol-iron complex is a ferroptosis inducer to inhibit triple-negative breast tumor growth

Hongting Zhao1, Meng Zhang2, Jinghua Zhang1

  • 1State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, 22 Hankou Road, Nanjing, 210093, China.

Cell & Bioscience
|May 13, 2023
PubMed
Abstract

Insights

Hinokitiol complexed with iron (Fe(hino)3) acts as a potent ferroptosis inducer, significantly reducing triple-negative breast cancer tumor growth. This novel iron complex shows therapeutic promise for cancer treatment.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Oncology

Background:

  • Ferroptosis is an iron-dependent cell death pathway crucial in various pathological processes.
  • Therapy-resistant cancers, especially metastatic ones, exhibit vulnerability to ferroptosis.
  • Targeting ferroptosis presents a promising therapeutic strategy in oncology.

Purpose of the Study:

  • To investigate the potential of hinokitiol-iron complex (Fe(hino)3) as a ferroptosis inducer.
  • To evaluate the efficacy of Fe(hino)3 in triple-negative breast cancer (TNBC) models.
  • To assess the safety profile of Fe(hino)3 for therapeutic applications.

Main Methods:

  • Complexation of hinokitiol with iron to form Fe(hino)3.
  • In vitro assessment of Fe(hino)3 as a ferroptosis inducer.
  • Evaluation of Fe(hino)3 efficacy in orthotopic TNBC tumor models.
  • Analysis of Fe(hino)3-induced lipid peroxidation and tumor size reduction.
  • Safety evaluation of Fe(hino)3 at tested dosages.

Main Results:

  • Fe(hino)3 demonstrated significantly enhanced ferroptosis induction compared to iron alone (nearly 1000-fold increase).
  • Fe(hino)3-induced ferroptosis was inhibited by iron chelators, ferroptosis inhibitors, and antioxidants.
  • In vivo studies showed Fe(hino)3 significantly reduced TNBC tumor size by inducing lipid peroxidation.
  • No detrimental side effects were observed at the tested dosages, indicating a favorable safety profile.

Conclusions:

  • Fe(hino)3 functions as a potent ferroptosis inducer by promoting free radical production via the Fenton reaction within cells.
  • The complex exhibits significant therapeutic anti-TNBC activity.
  • Fe(hino)3 represents a promising novel therapeutic agent for treating triple-negative breast cancer.
Keywords:
Ferroptosis inducerHinokitiolIronLipid peroxidationTriple-negative breast cancer

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