N-hydroxycinnamide derivatives of osthole inhibit cell migration and invasion by suppressing smad2 and akt pathways in human colorectal adenocarcinoma cells

Ling Yu Liu, Wei Jan Huang, Feng Ming Ho, Ren-Jye Lin, Shyr Yi Lin, Fat Moon Suk, Yu Chih Liang

研究成果: 雜誌貢獻文章

12 引文 斯高帕斯(Scopus)

摘要

WJ1376-1 and WJ1398-1 are new synthetic compounds developed based on the structure of the Chinese herbal medicine osthole. Previously, we reported that WJ1376-1 and WJ1398-1 can induce cell-cycle arrest by activating ATR kinase (ataxia telangiectasia and rad3 related kinase) and inhibiting the phosphorylation of Aurora A kinase. In this study, we determined that WJ1376-1 and WJ1398-1 strongly inhibited the migration and invasion in human colorectal cancer cells at concentrations as low as 1 μM. In the transforming growth factor (TGF)-β-induced epithelial-mesenchymal transition model, WJ1376-1 and WJ1398-1 potently downregulated the transcription factor Snail1, the mesenchymal protein vimentin, and matrix metalloprotease-9, but upregulated the epithelial protein E-cadherin. WJ1376-1 and WJ1398-1 also inhibited the TGF-β-induced phosphorylation of Smad2 and of Akt at Ser 473, and the nuclear translocation of Smad2 was substantially lower in WJ1376-1- and WJ1398-1-treated cells than it was in control cells. In transient transfection experiments, we observed that WJ1376-1 and WJ1398-1 strongly inhibited TGF-β-stimulated activity of a Smad reporter. Finally, WJ1376-1 and WJ1398-1 blocked TGF-β-induced phosphorylation of the TGF-β Type I receptor (TGF-βRI). These results suggest that WJ1376-1 and WJ1398-1 inhibit cell migration and invasion by suppressing TGF-βRI phosphorylation and subsequently hindering both Smad2 and phosphatidylinositol 3-kinase/Akt signaling pathways.
原文英語
頁(從 - 到)1-8
頁數8
期刊Chemico-Biological Interactions
217
DOIs
出版狀態已發佈 - 六月 25 2014

ASJC Scopus subject areas

  • Toxicology

指紋 深入研究「N-hydroxycinnamide derivatives of osthole inhibit cell migration and invasion by suppressing smad2 and akt pathways in human colorectal adenocarcinoma cells」主題。共同形成了獨特的指紋。

  • 引用此