探討桂花有效物質調節前列腺癌之作用機制
李日馳1、陳忠賢1；2、謝佩坊1；3、吳俊賢1；2、林嘉祥1；2
1義大醫院外科部泌尿科；2 義守大學學士後醫學系；3中華醫事科技大學醫學檢驗生物技術系
Elucidation of the therapeutic role of osmanthus fragrans active compound in the regulation of prostate cancer
Ryh-Chyr Li1、Chung-Hsien Chen1；2、Pei-Fang Hsieh1；3、Chun-Hsien Wu1；2、Victor C. Lin1；2
Department of Urology, E-Da Hospital, Kaohsiung, Taiwan1;
School of Medicine for International Students, I-Shou University, Kaohsiung, Taiwan2;
Graduate Institute of Medical Laboratory Science and Biotechnology, Chung Hwa University of Medical, Tainan, Taiwan3
Purpose:
Advanced prostate cancer has higher mortality rate with complicated mechanisms. However, the effective treatment for advanced prostate cancer is still poor. Verbascoside, a major bioactive constituent of the Chinese herb from Osmanthus Fragrans, displays pharmacological properties by exhibiting anti-oxidative, anti-inflammatory, and anti-cancer activities. In addition, Verbascoside was proved effective for inhibiting the growth of colonic and hepatic carcinoma cells. However, the underlining function and mechanism of Verbascoside in human prostate cancer remains unclear. In addition, dysregulated TGF-β signaling leads to a cascade of events contributing to prostate oncogenesis, including up-regulated proliferation, epithelial-to-mesenchymal transition (EMT) and evasion of immune surveillance. Thus, the present study focused on evaluating the effects of purified Verbascoside on the growth of human prostate cancer in vitro, and possible molecular mechanisms.
Materials and Methods:
The human prostate cancer cell line, PC-3 and Du-145, was incubated with various concentrations of Verbascoside (0.1, 1, 10uM) for 24h followed by series of biological examination. Cell viability, proliferation and toxicity was accessed by MTT, trypan blue exclusion assay and LDH assay. Cell migration was accessed by wound healing assay. Western blot and immunofluorescence staining were used to detect the expression of TGF β1/Smad signal related proteins and epithelial-mesenchymal transition (EMT).
Results:
It was found that Verbascoside treatment significantly inhibited cell proliferation, and cell migration. In addition, Verbascoside significantly reduced the expression of HMGB1 in prostate cells. It significantly decreased TGF-β1 signaling. TGF-β1 downstream signal regulators Smad 2/3 were reduced, and the inhibitor Smad 7 was increased. Further investigating the EMT markers showed that Verbascoside decrease EMT, it decreases the expression of α-SMA and increase expression of E-cadherin.
Conclusion:
In the present study, Verbascoside was found to show anticancer effects on in vitro cultured prostate cancer PC-3 and Du-145 cells. These effects were demonstrated by suppressed cell proliferation, tumor invasion and EMT. The underlying mechanisms may be associated with modulating EMT process by down-regulating HMGB1-induced TGF β1/Smad pathway.