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Targeting FOXM1/Cystathionine-β-Synthase Axis by Brusatol Inhibits Lung Cancer Malignant Progression
Yutong Wu1, Haipeng Feng2,3, Yichuan Wang3
1Department of Oncology, Affiliated Zhongshan Hospital of Dalian University, Dalian, China.
Phytotherapy Research : PTR
|February 20, 2026
Summary
Brusatol, a natural compound, directly targets and degrades FOXM1, inhibiting lung cancer progression. This blocks the FOXM1/CBS signaling pathway, offering a new therapeutic strategy for lung cancer.
Area of Science:
- Pharmacology
- Molecular Biology
- Oncology
Background:
- Brusatol (BRU) shows antitumor potential in lung cancer.
- Its molecular targets and mechanisms in lung cancer require further investigation.
Purpose of the Study:
- To elucidate the molecular targets and mechanisms of Brusatol in lung cancer.
- To investigate Brusatol's interaction with FOXM1 and its downstream effects.
Main Methods:
- Label-free quantitative proteomic analysis.
- Cell proliferation, apoptosis, and cytotoxicity assays (colony formation, PI staining, CCK8).
- Western blot, qRT-PCR, SA-based pulldown, CTSA, and molecular docking.
Main Results:
- Brusatol directly interacts with FOXM1, causing its degradation and suppressing lung cancer progression.
- FOXM1 enhances Cystathionine beta-synthase (CBS) expression in lung cancer.
- Brusatol inhibits the FOXM1/CBS signaling axis in vitro, in vivo, and in patient-derived organoids.
Conclusions:
- Brusatol acts as a novel FOXM1 inhibitor.
- Inhibition of the FOXM1/CBS axis by Brusatol presents a potential therapeutic strategy for lung cancer.
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