Celastrol inhibits TGF-β1-induced epithelial-mesenchymal transition by inhibiting Snail and regulating E-cadherin expression

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-beta 1) 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 (MOCK) and A549 cell lines show that TGF-beta 1-mediated the EMT in epithelial cells; however, celastrol markedly inhibited TGF-beta 1-induced morphologic changes, Snail upregulation, and E-cadherin expression. Migration and invasion assays revealed that celastrol completely inhibited TGF-beta 1-mediated cellular migration in both cell lines. These findings indicate that celastrol downregulates Snail expression, thereby inhibiting TGF-beta 1-induced EMT in MDCK and A549 cells. Thus, our findings provide new evidence that celastrol suppresses lung cancer invasion and migration by inhibiting TGF-beta 1-induced EMT. (C) 2013 Elsevier Inc. All rights reserved.