title: Resveratrol inhibits LPS-induced epithelial-mesenchymal transition in mouse melanoma model.
abstract: 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.
authors.affiliation: Department of Microbiology, School of Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Man-Chin
authors.initials: MC
authors.lastname: Chen
authors.forename: Wen-Wei
authors.initials: WW
authors.lastname: Chang
authors.forename: Yu-Diao
authors.initials: YD
authors.lastname: Kuan
authors.forename: Song-Tao
authors.initials: ST
authors.lastname: Lin
authors.forename: Hui-Chun
authors.initials: HC
authors.lastname: Hsu
authors.forename: Che-Hsin
authors.initials: CH
authors.lastname: Lee
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D014408:Biomarkers, Tumor / Q000378:metabolism; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008070:Lipopolysaccharides / Q000378:metabolism; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000556:secondary; D051379:Mice; D008809:Mice, Inbred C3H; D016328:NF-kappa B / Q000378:metabolism; D000077185:Resveratrol; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000071250:Snail Family Transcription Factors; D013267:Stilbenes / Q000008:administration & dosage*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D014408:Biomarkers, Tumor; D015820:Cadherins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D000071250:Snail Family Transcription Factors; D013267:Stilbenes; D014157:Transcription Factors; D000077185:Resveratrol