Department of Urology, E-Da Hospital, Kaohsiung, Taiwan.
Department of Chemical Engineering and Institute of Biotechnology and Chemical Engineering, I-Shou University, Kaohsiung, Taiwan.
Environ Toxicol. 2021 Jun;36(6):1080-1089. doi: 10.1002/tox.23107. Epub 2021 Feb 1.
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.
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.
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.
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.
前列腺癌在男性中具有较高的死亡率和转移率。不幸的是，对于晚期前列腺癌患者，有效的治疗方法仍然缺乏。毛蕊花糖苷是一种苯乙醇苷类化合物，具有多种药理作用，如抗癌活性。本研究旨在评估纯化毛蕊花糖苷对人前列腺癌的影响及其相关的分子机制。
用不同浓度的毛蕊花糖苷（0.1、1、10μM）处理人前列腺癌细胞系 Du-145 和 PC-3 24 小时，然后用 MTT 和台盼蓝排斥试验检测细胞活力。通过划痕愈合试验和 Transwell 系统评估细胞迁移和侵袭能力。Western blot 和免疫荧光染色用于检测上皮间质转化（EMT）相关因子、转化生长因子（TGF-β）/Smad 信号通路成分以及高迁移率族蛋白（HMGB）/晚期糖基化终产物受体（RAGE）轴的表达。
毛蕊花糖苷处理显著抑制了 Du-145 和 PC-3 细胞的增殖、迁移和侵袭能力。结果显示，毛蕊花糖苷降低了 EMT 启动子 Snail 和 Slug 的表达，增加了 E-钙黏蛋白的表达。此外，毛蕊花糖苷还下调了α-平滑肌肌动蛋白的表达水平。此外，我们发现 TGF-β 通路受到抑制，表现为 I 型和 II 型 TGF-β受体表达减少，磷酸化 Smad2/3 减少，Smad7 表达增加。我们的数据表明，HMGB1/RAGE 轴的抑制介导了 TGF-β 信号的下调。
毛蕊花糖苷通过抑制 HMGB1/RAGE 抑制 TGF-β 相关的 EMT 进展，减轻前列腺癌细胞的增殖和侵袭能力。综上所述，我们的研究结果表明，毛蕊花糖苷可能是前列腺癌患者有益的膳食补充剂。
