Related Experiment Video
Updated: Mar 18, 2026
Modeling Brain Metastasis Via Tail-Vein Injection of Inflammatory Breast Cancer Cells
Published on: February 4, 2021
Brusatol inhibits metastasis of triple-negative breast cancer through metabolic reprogramming
Xuan Yu1,2, Xueling Diao1,2, Xiaokai Fan1,3
1Shenzhen Laboratory of Tumor Cell Biology, Institutes of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
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, NADPH/NADP+ 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.
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.
Insights
Brusatol (BRU) effectively targets metabolic adaptation in triple-negative breast cancer (TNBC) cells, reducing metastasis and cell death. This natural compound shows potential for enhancing anti-cancer therapies with reduced toxicity.
Area of Science:
- Oncology
- Metabolic Research
- Natural Products Chemistry
Background:
- Triple-negative breast cancer (TNBC) presents aggressive metastasis and poor prognosis.
- Current chemotherapy for TNBC faces limitations due to toxicity and drug resistance.
- Brusatol (BRU), a natural compound, has shown anti-tumor effects but its anti-metastatic mechanisms and impact on metabolic reprogramming remain unexplored.
Purpose of the Study:
- To investigate the anti-metastatic mechanism of Brusatol (BRU) in triple-negative breast cancer (TNBC).
- To explore how BRU targets the metabolic adaptation of detached TNBC cells.
Main Methods:
- Assessed BRU's suppressive effects using LDH release assays, trypan blue staining, tumor spheroid culture, and metastasis assays.
- Utilized global metabolomics, NADPH/NADP+ measurements, ROS detection, and gene expression analysis to evaluate metabolic and redox alterations.
Main Results:
- BRU induced membrane damage and cell death in extracellular matrix-detached TNBC cells, suppressing metastasis in vivo.
- Metabolomics revealed BRU inhibits key metabolic pathways (PPP, glycolysis, TCA cycle), reducing NADPH levels and increasing redox stress.
Conclusions:
- BRU targets metabolic plasticity in TNBC cells, demonstrating anti-metastatic potential.
- BRU may serve as an effective adjuvant therapy to improve anti-tumor efficacy and mitigate chemotherapy-associated toxicity.
Related Concept Videos
02:30Metastasis
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
02:30Metastasis