Arctigenin represses TGF-β-induced epithelial mesenchymal transition in human lung cancer cells

Biochem Biophys Res Commun. 2017 Nov 18;493(2):934-939. doi: 10.1016/j.bbrc.2017.09.117. Epub 2017 Sep 23.

Abstract

Arctigenin (ARC) is a lignan that is abundant in Asteraceae plants, which show anti-inflammatory and anti-cancer activities. The current study investigated whether ARC affects cancer progression and metastasis, focusing on EMT using invasive human non-small cell lung cancer (NSCLC) cells. No toxicity was observed in the cells treated with different doses of ARC (12-100 μM). The treatment of ARC repressed TGF-β-stimulated changes of metastatic morphology and cell invasion and migration. ARC inhibited TGF-β-induced phosphorylation and transcriptional activity of smad2/3, and expression of snail. ARC also decreased expression of N-cadherin and increased expression of E-cadherin in dose-dependent and time-dependent manners. These changes were accompanied by decreased amount of phospho-smad2/3 in nucleus and nuclear translocation of smad2/3. Moreover, ARC repressed TGF-β-induced phosphorylation of ERK and transcriptional activity of β-catenin. Our data demonstrate anti-metastatic activity of ARC in lung cancer model.

Keywords: Arctigenin; EMT; Lung cancer; Metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Asteraceae / chemistry
  • Cadherins / metabolism
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Survival / drug effects
  • Epithelial-Mesenchymal Transition / drug effects*
  • Furans / chemistry
  • Furans / pharmacology*
  • Humans
  • Lignans / chemistry
  • Lignans / pharmacology*
  • Lung / drug effects
  • Lung / metabolism
  • Lung / pathology
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Neoplasm Invasiveness / pathology
  • Neoplasm Invasiveness / prevention & control
  • Phosphorylation / drug effects
  • Smad2 Protein / metabolism
  • Smad3 Protein / metabolism
  • Transforming Growth Factor beta / metabolism*
  • beta Catenin / metabolism

Substances

  • Antineoplastic Agents, Phytogenic
  • Cadherins
  • Furans
  • Lignans
  • SMAD2 protein, human
  • SMAD3 protein, human
  • Smad2 Protein
  • Smad3 Protein
  • Transforming Growth Factor beta
  • beta Catenin
  • arctigenin