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Brusatol Inhibits Proliferation and Metastasis of Colorectal Cancer by Targeting and Reversing the RhoA/ROCK1 Pathway

Rui-Jin Lu1, Guo-Zhi Zhao2, Rong Jiang1

  • 1Lab of Stem Cell and Tissue Engineering, Department of Histology and Embryology, Chongqing Medical University, Chongqing, China.

Biomed Research International
|June 1, 2022
PubMed

Insights

Brusatol (BRU) inhibits colorectal cancer cell proliferation and metastasis. This study reveals BRU influences epithelial-mesenchymal transition (EMT) via the RhoA/ROCK1 pathway, offering a potential new strategy for colon cancer treatment.

Area of Science:

  • Pharmacology
  • Oncology
  • Molecular Biology

Background:

  • Brusatol (BRU), derived from Brucea javanica oil, exhibits known antitumor properties.
  • The specific mechanisms of brusatol's effects on colorectal cancer remain largely undefined.
  • Investigating BRU's impact on colon cancer proliferation and metastasis is crucial.

Purpose of the Study:

  • To investigate the effects of brusatol on colorectal cancer cell proliferation, migration, and invasion.
  • To elucidate the underlying molecular mechanisms, including the role of epithelial-mesenchymal transition (EMT) and the RhoA/ROCK1 pathway.
  • To validate the antitumor effects of brusatol in an in vivo model.

Main Methods:

  • Cell proliferation was assessed using CCK-8 and colony formation assays.
  • Cell migration and invasion were evaluated through scratch and Transwell assays.
  • Protein expression levels of RhoA, ROCK1, and EMT markers were analyzed via Western blot.
  • In vivo efficacy was tested using a xenotransplantation model.

Main Results:

  • Brusatol significantly inhibited colorectal cancer cell proliferation, migration, and invasion in vitro.
  • BRU treatment led to decreased expression of RhoA, ROCK1, and EMT markers (N-cadherin, Vimentin, MMP2, MMP9), with increased e-cadherin.
  • In vivo experiments confirmed brusatol's antitumor effect on colon cancer, consistent with in vitro findings.

Conclusions:

  • Brusatol demonstrates significant inhibitory effects on colorectal cancer proliferation and metastasis.
  • The mechanism involves the inhibition of EMT through the RhoA/ROCK1 signaling pathway.
  • Brusatol shows potential as a therapeutic agent for colorectal cancer.

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