Anti-Metastatic Effects of Lupeol via the Inhibition of MAPK/ERK Pathway in Lung Cancer

Anticancer Agents Med Chem. 2021;21(2):201-206. doi: 10.2174/1871520620666200424131548.


Background and objective: ERK pathway is one of the most crucial pathways in lung cancer metastasis. Targeting its pathway is decisive in lung cancer research. Thus, this study demonstrated for the first time for significant and selective anti-metastatic effects of lupeol against lung cancer A549 cells via perturbations in the ERK signaling pathway.

Materials and methods: Human protein targets of lupeol were predicted in silico. Migration and cytotoxicity assays were carried out in vitro. Expression levels of proteins Erk1/2 and pErk1/2 were ensured using Enzyme- Linked Immunosorbent Assay (ELISA). Semi-quantitative RT-PCR technique was used to estimate changes in crucial mesenchymal marker gene expression levels of N-cadherin and vimentin.

Results: Lupeol was found to target ERK and MEK proteins effectively. Despite having no cytotoxic effects, lupeol also significantly inhibited cell migration in A549 cells with decreased expression of the pErk1/2 protein along with N-cadherin and vimentin genes.

Conclusion: Lupeol inhibits cell migration, showed no cytotoxic effects on A549 cells, decreased pErk1/2 and EMT gene expression. Thus, it can serve as a potential ERK pathway inhibitor in lung cancer therapeutics.

Keywords: Cancer; ERK; Epithelial-Mesenchymal Transition (EMT) marker genes; lupeol; metastasis; reverse docking.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Antineoplastic Agents / pharmacology*
  • Cell Movement / drug effects
  • Epithelial-Mesenchymal Transition / drug effects
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • MAP Kinase Signaling System / drug effects*
  • Neoplasm Invasiveness / pathology
  • Neoplasm Invasiveness / prevention & control
  • Pentacyclic Triterpenes / pharmacology*


  • Antineoplastic Agents
  • Pentacyclic Triterpenes
  • lupeol