title: Celastrol inhibits TGF-β1-induced epithelial-mesenchymal transition by inhibiting Snail and regulating E-cadherin expression.
abstract: The epithelial-mesenchymal transition (EMT) is a pivotal event in the invasive and metastatic potentials of cancer progression. Celastrol inhibits the proliferation of a variety of tumor cells including leukemia, glioma, prostate, and breast cancer; however, the possible role of celastrol in the EMT is unclear. We investigated the effect of celastrol on the EMT. Transforming growth factor-beta 1 (TGF-β1) induced EMT-like morphologic changes and upregulation of Snail expression. The downregulation of E-cadherin expression and upregulation of Snail in Madin-Darby Canine Kidney (MDCK) and A549 cell lines show that TGF-β1-mediated the EMT in epithelial cells; however, celastrol markedly inhibited TGF-β1-induced morphologic changes, Snail upregulation, and E-cadherin expression. Migration and invasion assays revealed that celastrol completely inhibited TGF-β1-mediated cellular migration in both cell lines. These findings indicate that celastrol downregulates Snail expression, thereby inhibiting TGF-β1-induced EMT in MDCK and A549 cells. Thus, our findings provide new evidence that celastrol suppresses lung cancer invasion and migration by inhibiting TGF-β1-induced EMT.
authors.affiliation: Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Hyereen
authors.initials: H
authors.lastname: Kang
authors.forename: Minjae
authors.initials: M
authors.lastname: Lee
authors.forename: Sung-Wuk
authors.initials: SW
authors.lastname: Jang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D015820:Cadherins / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D004285:Dogs; D058750:Epithelial-Mesenchymal Transition; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism; D061985:Madin Darby Canine Kidney Cells; D009361:Neoplasm Invasiveness; D053978:Pentacyclic Triterpenes; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D015820:Cadherins; D053978:Pentacyclic Triterpenes; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D053773:Transforming Growth Factor beta1; D014315:Triterpenes; C050414:celastrol
keywords: Celastrol; E-cadherin; EMT; Invasion; Snail