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 mu M). The treatment of ARC repressed TGF-beta-stimulated changes of metastatic morphology and cell invasion and migration. ARC inhibited TGF-beta-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-beta-induced phosphorylation of ERR and transcriptional activity of beta-catenin. Our data demonstrate anti metastatic activity of ARC in lung cancer model. (C) 2017 Elsevier Inc. All rights reserved.