Isorhamnetin inhibited migration and invasion via suppression of Akt/ERK-mediated epithelial-to-mesenchymal transition (EMT) in A549 human non-small-cell lung cancer cells

Biosci Rep. 2019 Sep 20;39(9):BSR20190159. doi: 10.1042/BSR20190159. Print 2019 Sep 30.


In the present study, we investigated the potential effects of Isorhamnetin on the growth and metastasis of A549 human lung cancer cells, as well as the underlying mechanism. Treatment with Isorhamnetin exhibited a dose- and time-dependent inhibition on A549 cell proliferation. Furthermore, the cell adhesion and Transwell assay showed that treatment with Isorhamnetin (2.5, 5, and 10 μM) for 48 h resulted in a significant inhibition effect on cell adhesion, invasion and migration of A549 cells, depending on concentration, which was associated with the suppression of matrix metalloproteinase (MMP)-2 and MMP-9 activity and protein expression. Moreover, Isorhamnetin effectively suppressed the expressions of epithelial-to-mesenchymal transition (EMT) markers, as evidenced by the down-regulation of N-cadherin, vimentin and snail, as well as up-regulation of E-cadherin protein expression. Additionally, these inhibitions were mediated by interrupting AKT/ERK1/2 signaling pathways. Taken together, the results of the current study demonstrated that Isorhamnetin may become a good anti-metastastic agent against lung cancer A549 cell line by the suppression of EMT via interrupting Akt/ERK1/2 signaling pathway.

Keywords: Akt/ERK1/2; Epithelial-mesenchymal transition (EMT); Isorhamnetin; Lung cancer; Metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Animals
  • Antioxidants / pharmacology*
  • Cadherins / metabolism
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Adhesion / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Epithelial-Mesenchymal Transition / drug effects*
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • MAP Kinase Signaling System / drug effects
  • Matrix Metalloproteinase 2 / drug effects
  • Matrix Metalloproteinase 9 / drug effects
  • Neoplasm Invasiveness / pathology
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins c-akt / metabolism
  • Quercetin / analogs & derivatives*
  • Quercetin / pharmacology
  • Snail Family Transcription Factors / metabolism
  • Vimentin / metabolism


  • Antioxidants
  • Cadherins
  • SNAI1 protein, human
  • Snail Family Transcription Factors
  • Vimentin
  • 3-methylquercetin
  • Quercetin
  • Proto-Oncogene Proteins c-akt
  • MMP2 protein, human
  • Matrix Metalloproteinase 2
  • MMP9 protein, human
  • Matrix Metalloproteinase 9