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

Abstract

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 pharmacological 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-β)/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 prostate cancer via downregulation of TGF-β-associated EMT progression through Chun-Hsien Wu and Chung-Hsien Chen contributed equally to this study.

Olive Mill Wastewater Inhibits Growth and Proliferation of Cisplatin- and Gemcitabine-Resistant Bladder Cancer Cells In Vitro by Down-Regulating the Akt/mTOR-Signaling Pathway

“…In fact, other phenols found in OMWW have been shown to have antitumorigenic properties. Verbascoside has recently been reported to mitigate cell proliferation and aggressiveness of prostate cancer [40], and novel data emphasize the role of oleuropein in the reduction of cisplatin resistance in ovarian cancer [41]. The polyphenol composition in OMWW may therefore act synergistically on tumor cells.…”

Natural Compounds for Counteracting Nonalcoholic Fatty Liver Disease (NAFLD): Advantages and Limitations of the Suggested Candidates

“…In vitro: Du-145 and PC-3 cell lines Reduction in α-SMA expression [81] In vivo: renal-fibrosis-induced rats Reduction in COL-I, α-SMA, and TIMP2 Decreased macrophage infiltration [82]…”

“…In the human prostate cancer cell lines Du-145 and PC-3, verbascoside was able to downregulate the expression level of alpha-smooth muscle actin by inhibiting the transforming growth factor (TGF-β)/Smad signaling pathway [ 81 ].…”

Verbascoside—A Review of Its Antitumor Activities

“…Treatment with VERB significantly prevented cell proliferation, and migration capabilities of men prostate tumor cell line (e.g. PC-3 cells and Du-145) by suppression of HMGB1/RAGE pathway, which resulted in downregulation of TGF-β-associated epithelial-mesenchymal transition (EMT) progression [73].…”