2. Academic Validation
  3. 4, 9-dihydroxy-α-lapachone as a potent antiproliferation agent for triple-negative breast cancer via ferroptosis

4, 9-dihydroxy-α-lapachone as a potent antiproliferation agent for triple-negative breast cancer via ferroptosis

  • Fitoterapia. 2025 Jun:183:106567. doi: 10.1016/j.fitote.2025.106567.
Zhong He 1,  Hui Long 2,  Hongyue Ma 2,  Wanrong Ran 3,  Yinhong Song 4,  Wenjuan Shang 5,  Junhui Wang 6,  Ye Qin 7,  Zhangshuang Deng 8
Affiliations

Affiliations

  • 1 Hubei Key Laboratory of Natural Products Research and Development, College of Biological and Pharmaceutical Sciences, China Three Gorges University, Yichang 443002, China; Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, College of Basic Medical Sciences, China Three Gorges University, Yichang 443002, China; State Key Laboratory of Drug Research, Molecular Imaging Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
  • 2 Hubei Key Laboratory of Natural Products Research and Development, College of Biological and Pharmaceutical Sciences, China Three Gorges University, Yichang 443002, China.
  • 3 Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, College of Basic Medical Sciences, China Three Gorges University, Yichang 443002, China.
  • 4 Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, College of Basic Medical Sciences, China Three Gorges University, Yichang 443002, China; Institute of Infection and Inflammation, China Three Gorges University, Yichang 443002, China. Electronic address: syh728@ctgu.edu.cn.
  • 5 Medical College, Hubei Three Gorges Polytechnic, Yichang 443000, China.
  • 6 State Key Laboratory of Tree Genetics and Breeding, Key Laboratory of Tree Breeding and Cultivation of State Forestry Administration, Research Institute of Forestry, Chinese Academy of Forestry, Beijing 100091, China. Electronic address: wangjh@caf.ac.cn.
  • 7 Hubei Key Laboratory of Natural Products Research and Development, College of Biological and Pharmaceutical Sciences, China Three Gorges University, Yichang 443002, China; Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, College of Basic Medical Sciences, China Three Gorges University, Yichang 443002, China; State Key Laboratory of Drug Research, Molecular Imaging Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. Electronic address: ycqinye@163.com.
  • 8 Hubei Key Laboratory of Natural Products Research and Development, College of Biological and Pharmaceutical Sciences, China Three Gorges University, Yichang 443002, China. Electronic address: dzs163@163.com.
PMID: 40280251 DOI: 10.1016/j.fitote.2025.106567
Abstract

Triple-negative breast Cancer (TNBC) is the most aggressive and malignant breast Cancer. Ferroptosis is an oxidative, iron-dependent form of regulated cell death. Ferroptosis-targeted therapies is a promising approach to improving treatment outcomes of TNBC. Combining death pathway inhibitors with relevant indices for Ferroptosis and LipROS, this study uncovered that a natural product of 4, 9-dihydroxy-α-lapachone (DLN) from Catalpa bungei "jinsi" exhibited in vitro and in vivo inhibitory activity against TNBC via Ferroptosis. The molecular mechanism is an activation of the FTH1 led to iron overload, and then inhibition of cysteine-glutamate antiporter (system Xc-) and GPX4, which further sensitized TNBC cells to Ferroptosis. This study clarified the pathway of DLN-induced cell death in TNBC treatment and exhibited its potential as therapeutic agent for TNBC.

Keywords

4, 9-dihydroxy-α-lapachone; Ferroptosis; GPX4; TNBC.

Figures
Products