Verbascoside inhibits the epithelial-mesenchymal transition of prostate cancer cells through high-mobility group box 1/receptor for advanced glycation end-products/TGF-β pathway

摘要

Introduction: Prostate cancer has significant mortality and metastasis rate in the : male. Unfortunately, effective treatment for patients with advanced prostate cancer is still lacking. Verbascoside, a phenylethanoid glycoside, displays various pharmaco- h logical properties, such as the anti-cancer activities. The present study aimed to evaluate the effects of purified verbascoside on human prostate cancer and the ; associated molecular mechanisms. Materials and Methods: The human prostate cancer cell lines, Du-145 and PC-3, ' were treated with various concentrations of verbascoside (0.1, 1, 10 μM) for 24 h : followed by the examination of cell viability using MTT and trypan blue exclusion ; assays. Cell migration and invasion capacities were assessed by wound healing assay ; and transwell system. Western blot and immunofluorescence staining were used to ; detect the expression of epithelial-mesenchymal transition (EMT)-associated factors, components of transforming growth factor (TGF-p)/Smad signaling, and high-mobility : group box (HMGB)/receptor for advanced glycation end-products (RAGE) axis. « Results: Verbascoside treatment significantly inhibited cell proliferation, migration, and invasion abilities of Du-145 and PC-3 cells. We showed that verbascoside decreased the expression of EMT promotors, Snail and Slug, and increased the expression of E-cadherin. Moreover, the expression level of alpha-smooth muscle actin was downregulated by verbascoside as well. Besides, we found that the TGF-β pathway was suppressed, which was demonstrated by the diminished expression of type Ⅰ and Ⅱ TGF-β receptors and phosphorylated Smad2/3 along with the upregulated Smad7. Our data suggested that this downregulation of TGF-β signaling was mediated by repression of HMGB 1 (HMGB1)/RAGE axis. Conclusion: Verbascoside mitigated the cell proliferation and aggressiveness of pros-tate cancer via downregulation of TGF-p-associated EMT progression through HMGB1/RAGE suppression. Collectively, our findings revealed that verbascoside may be a beneficial dietary supplement for prostate cancer patients.