2. Academic Validation
  3. Hinokitiol-iron complex is a ferroptosis inducer to inhibit triple-negative breast tumor growth

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

  • Cell Biosci. 2023 May 13;13(1):87. doi: 10.1186/s13578-023-01044-0.
Hongting Zhao # 1,  Meng Zhang # 2,  Jinghua Zhang 1,  Zichen Sun 1,  Wenxin Zhang 1,  Weichen Dong 1,  Chen Cheng 1,  Yongzhong Yao 3,  Kuanyu Li 4
Affiliations

Affiliations

  • 1 State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, 22 Hankou Road, Nanjing, 210093, China.
  • 2 Department of General Surgery, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, 210008, China.
  • 3 Department of General Surgery, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, 210008, China. [email protected].
  • 4 State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, 22 Hankou Road, Nanjing, 210093, China. [email protected].
  • # Contributed equally.
PMID: 37179385 DOI: 10.1186/s13578-023-01044-0
Abstract

Background: Ferroptosis is a unique cell death, dependent on iron and phospholipid peroxidation, involved in massive processes of physiopathology. Tremendous attention has been caught in oncology, particularly for those therapy-resistant cancers in the mesenchymal state prone to metastasis due to their exquisite vulnerability to Ferroptosis. Therefore, a therapeutical Ferroptosis inducer is now underway to be exploited.

Results: A natural compound, hinokitiol (hino), has been considered to be an iron chelator. We have a novel finding that hino complexed with iron to form Fe(hino)3 can function as a Ferroptosis inducer in vitro. The efficiency, compared with the same concentration of iron, increases nearly 1000 folds. Other iron chelators, Ferroptosis inhibitors, or antioxidants can inhibit Fe(hino)3-induced Ferroptosis. The complex Fe(hino)3 efficacy is further confirmed in orthotopic triple-negative breast Cancer (TNBC) tumor models that Fe(hino)3 significantly boosted lipid peroxidation to induce Ferroptosis and significantly reduced the sizes of TNBC cell-derived tumors. The drug's safety was also evaluated, and no detrimental side effects were found with the tested dosage.

Conclusions: When entering cells, the chelated iron by hinokitiol as a complex Fe(hino)3 is proposed to be redox-active to vigorously promote the production of free radicals via the Fenton reaction. Thus, Fe(hino)3 is a Ferroptosis inducer and, therapeutically, exhibits anti-TNBC activity.

Keywords

Ferroptosis inducer; Hinokitiol; Iron; Lipid peroxidation; Triple-negative breast cancer.

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