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

Cell & Bioscience

Research

Meng Zhang¹  Yongzhong Yao¹  Hongting Zhao²  Weichen Dong²  Zichen Sun²  Jinghua Zhang²  Wenxin Zhang²  Chen Cheng²  Kuanyu Li² 

[1] Department of General Surgery, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, 210008, Nanjing, China;State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, 22 Hankou Road, 210093, Nanjing, China;

关键词: Ferroptosis inducer;    Iron;    Hinokitiol;    Triple-negative breast cancer;    Lipid peroxidation;   

DOI  :  10.1186/s13578-023-01044-0

 received in 2023-01-31, accepted in 2023-05-03,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundFerroptosis 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.ResultsA 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.ConclusionsWhen 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.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

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