The Ferroptosis-inducing Compounds in Triple Negative Breast Cancer
10.16476/j.pibb.2024.0344
- VernacularTitle:诱导三阴性乳腺癌发生铁死亡的化合物
- Author:
Xin-Die WANG
1
;
Da-Li FENG
1
;
Xiang CUI
2
;
Su ZHOU
2
;
Peng-Fei ZHANG
3
;
Zhi-Qiang GAO
3
;
Li-Li ZOU
2
;
Jun WANG
1
Author Information
1. Hubei Provincial Clinical Research Center for Precise Prevention and Treatment of Gastrointestinal Cancer in the Elderly & Cancer Prevention Office, The Second People’s Hospital of China Three Gorges University & The Second People’s Hospital of Yichang, Yichang 443003, China
2. Key Laboratory of Tumor Microenvironment and Immunotherapy at Three Gorges University & Yichang Key Laboratory of Infection and Inflammation, College of Basic Medical Sciences, China Three Gorges University, Yichang 443002, China
3. Department of Endocrinology, Affiliated Yiling Hospital of China Three Gorges University & Yiling People’s Hospital, Yichang 443100, China
- Publication Type:Journal Article
- Keywords:
ferroptosis;
triple-negative breast cancer;
lead compounds;
traditional Chinese medicine extracts;
system Xc-
- From:
Progress in Biochemistry and Biophysics
2025;52(4):804-819
- CountryChina
- Language:Chinese
-
Abstract:
Ferroptosis, a programmed cell death modality discovered and defined in the last decade, is primarily induced by iron-dependent lipid peroxidation. At present, it has been found that ferroptosis is involved in various physiological functions such as immune regulation, growth and development, aging, and tumor suppression. Especially its role in tumor biology has attracted extensive attention and research. Breast cancer is one of the most common female tumors, characterized by high heterogeneity and complex genetic background. Triple negative breast cancer (TNBC) is a special type of breast cancer, which lacks conventional breast cancer treatment targets and is prone to drug resistance to existing chemotherapy drugs and has a low cure rate after progression and metastasis. There is an urgent need to find new targets or develop new drugs. With the increase of studies on promoting ferroptosis in breast cancer, it has gradually attracted attention as a treatment strategy for breast cancer. Some studies have found that certain compounds and natural products can act on TNBC, promote their ferroptosis, inhibit cancer cells proliferation, enhance sensitivity to radiotherapy, and improve resistance to chemotherapy drugs. To promote the study of ferroptosis in TNBC, this article summarized and reviewed the compounds and natural products that induce ferroptosis in TNBC and their mechanisms of action. We started with the exploration of the pathways of ferroptosis, with particular attention to the System Xc--cystine-GPX4 pathway and iron metabolism. Then, a series of compounds, including sulfasalazine (SAS), metformin, and statins, were described in terms of how they interact with cells to deplete glutathione (GSH), thereby inhibiting the activity of glutathione peroxidase 4 (GPX4) and preventing the production of lipid peroxidases. The disruption of the cellular defense against oxidative stress ultimately results in the death of TNBC cells. We have also our focus to the realm of natural products, exploring the therapeutic potential of traditional Chinese medicine extracts for TNBC. These herbal extracts exhibit multi-target effects and good safety, and have shown promising capabilities in inducing ferroptosis in TNBC cells. We believe that further exploration and characterization of these natural compounds could lead to the development of a new generation of cancer therapeutics. In addition to traditional chemotherapy, we discussed the role of drug delivery systems in enhancing the efficacy and reducing the toxicity of ferroptosis inducers. Nanoparticles such as exosomes and metal-organic frameworks (MOFs) can improve the solubility and bioavailability of these compounds, thereby expanding their therapeutic potential while minimizing systemic side effects. Although preclinical data on ferroptosis inducers are relatively robust, their translation into clinical practice remains in its early stages. We also emphasize the urgent need for more in-depth and comprehensive research to understand the complex mechanisms of ferroptosis in TNBC. This is crucial for the rational design and development of clinical trials, as well as for leveraging ferroptosis to improve patient outcomes. Hoping the above summarize and review could provide references for the research and development of lead compounds for the treatment for TNBC.
