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Toosendanin, a natural product, inhibited TGF‐β1‐induced epithelial‐mesenchymal transition through ERK/Snail pathway
Author(s) -
Luo Weiwei,
Liu Xin,
Sun Wen,
Lu JinJian,
Wang Yitao,
Chen Xiuping
Publication year - 2018
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.6132
Subject(s) - epithelial–mesenchymal transition , vimentin , mapk/erk pathway , downregulation and upregulation , transforming growth factor , focal adhesion , cancer research , p38 mitogen activated protein kinases , chemistry , kinase , cell migration , a549 cell , microbiology and biotechnology , blot , signal transduction , biology , immunology , cell , biochemistry , immunohistochemistry , gene
Epithelial‐mesenchymal transition (EMT) plays important roles in the metastasis of solid tumors. In this study, the effect of toosendanin (TSN), a natural insecticide extracted from Melia toosendan Sieb et Zucc, on transforming growth factor ‐ β1 (TGF‐β1)‐induced EMT was investigated. EMT was induced by TGF‐β1 in A549 and H1975 lung cancer cells. The morphological alterations were observed with a microscopy. The protein expression and localization of EMT biomarkers were determined by Western blotting and immunofluorescence. The migration, invasion, and adhesion were determined by wound‐healing, transwell, and adhesion assays. TGF‐β1 treatment induced spindle‐shaped alterations of cells, upregulation of N‐cadherin, Vimentin, p‐ERK1/2, and downregulation of E‐cadherin. The abilities of migration, invasion, and adhesion were also enhanced. These effects were significantly reversed by TSN at very low concentration (<10 nM). Furthermore, silence Snail significantly reversed TGF‐β1‐induced EMT biomarkers. In addition, TGF‐β1‐induced phosphorylation of ERK1/2 without affecting p38 mitogen‐activated protein kinases and Jun N‐terminal kinase. PD98059 and U0126, inhibitors of ERK1/2, showed similar inhibitory effect to that of TSN. In summary, TSN significantly inhibited TGF‐β1‐induced EMT and migration, invasion, and adhesion through ERK/Snail pathway in lung cancer cells. This study provides novel anticancer effects and molecular mechanisms for TSN.