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. 2021 Jun;36(6):1080-1089.
doi: 10.1002/tox.23107. Epub 2021 Feb 1.

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

Chun-Hsien Wu  1   2   3 , Chung-Hsien Chen  1   2   3 , Pei-Fang Hsieh  1   4 , Yen-Hsi Lee  2   5 , Wade Wei-Ting Kuo  1   2 , Richard Chen-Yu Wu  1   6 , Chih-Hsin Hung  2 , Yu-Lin Yang  4   7 , Victor C Lin  1   6
Affiliations

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

Chun-Hsien Wu et al. Environ Toxicol. 2021 Jun.

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 HMGB1/RAGE suppression. Collectively, our findings revealed that verbascoside may be a beneficial dietary supplement for prostate cancer patients.

Keywords: HMGB1/RAGE axis; TGF-β signaling; Verbascoside; prostate cancer.

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References

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