Ursolic acid inhibits epithelial-mesenchymal transition by suppressing the expression of astrocyte-elevated gene-1 in human nonsmall cell lung cancer A549 cells

Anticancer Drugs. 2013 Jun;24(5):494-503. doi: 10.1097/CAD.0b013e328360093b.

Abstract

Lung cancer is one of the most death-related cancers worldwide. Ursolic acid (UA), a pentacyclic triterpene acid, has a wide range of anticancer functions such as proapoptosis, antiangiogenesis, and antimetastasis. This study was carried out to explore the inhibition mechanism of UA on metastasis of lung cancer A549 cells. First, we found that UA inhibited the metastasis of lung cancer cells in a concentration-dependent manner through an adhesion assay, a cell wound healing assay, and a transwell migration assay in vitro. In addition, after treatment with UA, the A549 cells showed decreased expression of astrocyte-elevated gene-1 (AEG-1) accompanied by upregulation of E-cadherin and downregulation of N-cadherin and vimentin, which have been reported to characterize the epithelial-mesenchymal transition (EMT). Further results also confirmed that the expression of vimentin was decreased by the siRNA technique to directly knock down AEG-1 expression, indicating that AEG-1 was involved in UA-mediated EMT inhibition. Furthermore, our results showed that UA suppressed the expression level of AEG-1 by repressing nuclear factor-κB signaling. Altogether, UA inhibited the EMT by suppressing the expression of AEG-1, correlating with inhibition of nuclear factor-κB in A549 cells. These findings suggested that UA was a potent anti-lung cancer agent, and it may be able to prevent invasion and metastasis of lung cancer cells.

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Cadherins / genetics
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Adhesion / drug effects
  • Cell Adhesion Molecules / genetics*
  • Cell Adhesion Molecules / metabolism
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • Epithelial-Mesenchymal Transition / drug effects*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology
  • Membrane Proteins
  • NF-kappa B / metabolism
  • RNA-Binding Proteins
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Triterpenes / pharmacology*
  • Ursolic Acid
  • Vimentin / genetics

Substances

  • Antineoplastic Agents, Phytogenic
  • Cadherins
  • Cell Adhesion Molecules
  • MTDH protein, human
  • Membrane Proteins
  • NF-kappa B
  • RNA-Binding Proteins
  • Triterpenes
  • Vimentin