2. Academic Validation
  3. Brusatol inhibits malignant phenotypes and lipid metabolism of osteosarcoma cells by regulating PI3K/AKT and MAPK pathways

Brusatol inhibits malignant phenotypes and lipid metabolism of osteosarcoma cells by regulating PI3K/AKT and MAPK pathways

  • Phytomedicine. 2025 Feb 12:139:156464. doi: 10.1016/j.phymed.2025.156464.
Xuhui Yuan 1,  Shaolin Yu 1,  Lan Lin 1,  Yang Chen 1,  Zhaoyang Wu 1,  Xinyu Fang 2,  Wenming Zhang 3
Affiliations

Affiliations

  • 1 Department of Orthopaedic Surgery, the First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, PR China; Department of Orthopaedic Surgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou 350212, PR China; Fujian Provincial Institute of Orthopaedics, the First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, PR China.
  • 2 Department of Orthopaedic Surgery, the First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, PR China; Department of Orthopaedic Surgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou 350212, PR China; Fujian Provincial Institute of Orthopaedics, the First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, PR China. Electronic address: fangxinyu0417@fjmu.edu.cn.
  • 3 Department of Orthopaedic Surgery, the First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, PR China; Department of Orthopaedic Surgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou 350212, PR China; Fujian Provincial Institute of Orthopaedics, the First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, PR China. Electronic address: zhangwm0591@fjmu.edu.cn.
PMID: 39970856 DOI: 10.1016/j.phymed.2025.156464
Abstract

Background: Osteosarcoma (OS), the most frequent type of primary bone Cancer, has a poor prognosis in metastatic cases, with overall 5-year survival rates stagnating at 20 %-30 %. This highlights the critical need for innovative therapies to address the significant survival gap between metastatic and non-metastatic cases. Brusatol (BRU), a compound extracted from Brucea javanica, has shown promising anti-tumor properties in various cancers; however, its effects on OS have yet to be investigated.

Purpose: To investigate the anti-tumor mechanisms of BRU in OS and evaluate its potential therapeutic efficacy, with a particular focus on its impact on lipid metabolism and related signaling pathways.

Methods: In vitro experiments to assess the anti-tumor effects of BRU involved colony formation, CCK-8, Transwell analysis, as well as flow cytometry. RNA Sequencing was conducted to identify transcriptional changes in BRU-treated cells. The mechanism of action was investigated through analysis of lipid metabolism and key signaling pathways. Therapeutic efficacy and safety were evaluated in vivo using xenograft models.

Results: BRU significantly inhibited OS cell proliferation, migration, and invasion, while also inducing G2/M phase cell cycle arrest as well as promoting Apoptosis. Transcriptome analysis revealed that BRU affected lipid metabolism-related genes and suppressed the PI3K/Akt and MAPK pathways. BRU treatment reduced fatty acid synthase expression and free fatty acid content in OS cells. In vivo experiments demonstrated that BRU effectively restricted xenograft growth.

Conclusion: This study revealed that BRU exhibits potent anti-tumor effects in OS by modulating lipid metabolism through the PI3K/Akt and MAPK pathways.

Keywords

Brusatol; Lipid metabolism; MAPK pathway; Osteosarcoma; PI3K/AKT pathway.

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