Open AccessResveratrol inhibits LPS-induced epithelial-mesenchymal transition in mouse melanoma model
Author(s) -
Man-Chin Chen,
Wen–Wei Chang,
YuHsiang Kuan,
Song-Tao Lin,
HuiChun Hsu,
CheHsin Lee
Publication year - 2012
Publication title -
innate immunity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.921
H-Index - 69
eISSN - 1753-4267
pISSN - 1753-4259
DOI - 10.1177/1753425912436589
Subject(s) - resveratrol , epithelial–mesenchymal transition , signal transduction , chemistry , nf κb , cancer research , melanoma , metastasis , tlr4 , biology , microbiology and biotechnology , cancer , biochemistry , genetics
Epithelial to mesenchymal transition (EMT) has been linked to metastasis. Resveratrol exhibits potential antitumor activities; however, the inhibitory effects of resveratrol on the EMT of melanoma have not been demonstrated. Here, a new role for LPS in promoting EMT is described. LPS-induced EMT was identified by examining the markers of EMT. To assess the activation of NF-κB signal transduction pathway, we performed a reporter assay by using tumor cells transfected with the luciferase gene under the control of NF-κB response elements. The antitumor effects of resveratrol were evaluated in an experimental mouse metastasis tumor model. LPS increased N-cadherin and Snail expression and decreased zonula occludens-1 expression in a dose- and time-dependent manner. Meanwhile, LPS stimulated cell migration through activation of TLR4/NF-κB signal pathway. LPS-induced EMT is critical for inflammation-initiated metastasis. Nuclear translocation and transcriptional activity of p65 NF-κB, an important inducer of EMT, were inhibited by resveratrol. Resveratrol inhibited LPS-induced tumor migration and markers of EMT, significantly prolonged animal survival and reduced the tumor size. Thus, resveratrol plays an important role in the inhibition of LPS-induced EMT in mouse melanoma through the down-regulation of NF-κB activity. The data provide an insight into the mechanisms on the function of resveratrol during the processes of EMT.