ORIGINAL RESEARCH article
Front. Oncol.
Sec. Breast Cancer
Brusatol inhibits metastasis of triple-negative breast cancer through metabolic reprogramming
Provisionally accepted
- 1Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences (CAS), Shenzhen, China
- 2University of Chinese Academy of Social Sciences, Beijing, China
- 3Greater Bay Area Institute of Precision Medicine, Guangzhou, China
- 4Shenzhen Technology University College of Pharmacy, Shenzhen, China
- 5University of Macau Faculty of Social Sciences, Taipa, Macao, SAR China
- 6Sun Yat-Sen University, Guangzhou, China
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Background: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer (BC) characterized by a high risk of metastasis and poor prognosis. Current chemotherapy-based treatments are often limited by systemic toxicity and drug resistance. Brusatol (BRU), a natural compound with reported anti-tumor activity and low toxicity, has not been explored in the context of cancer metastasis or metabolic reprogramming. This study aimed to uncover the anti-metastatic mechanism of BRU by targeting the metabolic adaptation of detached TNBC cells. Methods: The suppressive effect of BRU was assessed via LDH release assays, trypan blue staining, tumor spheroid culture and spontaneous metastasis assays. To elucidate the underlying mechanisms, global metabolomics analysis, NADP/NADPH measurements, intracellular ROS detection by flow cytometry, and quantitative PCR for metabolic gene expression were applied to evaluate metabolic alterations and redox imbalance. Results: BRU promoted membrane damage and cell death in extracellular matrix (ECM)-detached TNBC cells and suppressed metastasis in vivo. Metabolomics analysis showed that BRU inhibited metabolic pathways, including the pentose phosphate pathway (PPP), glycolysis, and the tricarboxylic acid (TCA) cycle, while significantly reducing NADPH levels and exacerbating redox stress. This is a provisional file, not the final typeset article Conclusions: These findings suggest that BRU targets metabolic plasticity in TNBC cells, highlighting its potential as an adjuvant therapy to enhance anti-tumor efficacy while reducing chemotherapy-associated toxicity.
Keywords: breast cancer, Brusatol, metabolic reprogramming, natural compound, Pentose Phosphate Pathway
Received: 19 Sep 2025; Accepted: 16 Feb 2026.
Copyright: © 2026 Yu, Diao, Fan, Wang, Cheung, Liu and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Liang Chen
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