富含 aspalathin 的绿色南非钩麻提取物通过抑制 YAP 信号通路抑制人去势抵抗性前列腺癌细胞的迁移和侵袭。
Aspalathin-rich green Aspalathus linearis extract suppresses migration and invasion of human castration-resistant prostate cancer cells via inhibition of YAP signaling.
机构信息
Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli County 35053, Taiwan; Department of Life Science, National Central University, Taoyuan City 32001, Taiwan.
Department of Life Science, National Central University, Taoyuan City 32001, Taiwan.
出版信息
Phytomedicine. 2020 Apr;69:153210. doi: 10.1016/j.phymed.2020.153210. Epub 2020 Mar 18.
BACKGROUND
More than 80% of advanced prostate cancer (PCa) cases have bone metastasis, with a 5-year survival rate of 25%. Previously, we reported that GRT, a standardized, pharmaceutical-grade aspalathin-rich extract (12.78 g aspalathin/100 g extract), prepared from green rooibos produced from the leaves and fine stems of Aspalathus linearis, inhibits the proliferation of PCa cells, meriting this investigation to determine if GRT can suppress the migration and invasion of castration-resistant prostate cancer (CRPC) cells.
PURPOSE
In the present study, we investigated whether GRT extract can interfere with the migration and invasion of human CRPC cells.
METHODS
Transwell assays were used to explore the effects of GRT on the migration and invasion of CRPC cells. Micro-Western Array (MWA) and Western blot analysis were carried out to unravel the underlying molecular mechanism(s).
RESULTS
Treatment with 25-100 μg/ml GRT suppressed the migration and invasion of LNCaP C4-2B and 22Rv1 CRPC cells. MWA and Western blot analysis indicated that GRT treatment suppressed the protein level of yes-associated protein (YAP), macrophage stimulating 1 protein (MST1), phospho-MST1/phospho-MST2 T183/T180, and paxillin, but increased the abundance of E-cadherin. Over-expression of YAP rescued the suppressive effects of GRT on migration and invasion of CRPC cells. Treatment with the major flavonoid of GRT - the C-glucosyl dihydrochalcone, aspalathin - at a concentration of 75-100 μg/ml also reduced the migration and invasion of CRPC cells, and the inhibition was partially rescued by YAP over-expression.
CONCLUSIONS
GRT treatment suppresses the migration and invasion of CRPC cells via inhibition of YAP signaling and paxillin.
背景
超过 80%的晚期前列腺癌（PCa）病例有骨转移，5 年生存率为 25%。此前，我们报道过 GRT，一种标准化的、药用级富含 aspalathin 的提取物（每 100 克提取物中含有 12.78 克 aspalathin），由 aspalathus linearis 的叶片和细茎制成的绿色 rooibos 制备，可抑制 PCa 细胞的增殖，值得进一步研究以确定 GRT 是否可以抑制去势抵抗性前列腺癌（CRPC）细胞的迁移和侵袭。
目的
在本研究中，我们研究了 GRT 提取物是否可以干扰人 CRPC 细胞的迁移和侵袭。
方法
使用 Transwell 测定法研究 GRT 对 CRPC 细胞迁移和侵袭的影响。微西方阵列（MWA）和 Western blot 分析用于揭示潜在的分子机制。
结果
用 25-100μg/ml 的 GRT 处理可抑制 LNCaP C4-2B 和 22Rv1 CRPC 细胞的迁移和侵袭。MWA 和 Western blot 分析表明，GRT 处理抑制了 yes 相关蛋白（YAP）、巨噬细胞刺激 1 蛋白（MST1）、磷酸化 MST1/磷酸化 MST2 T183/T180 和桩蛋白的蛋白水平，但增加了 E-钙粘蛋白的丰度。YAP 的过表达挽救了 GRT 对 CRPC 细胞迁移和侵袭的抑制作用。用 GRT 的主要类黄酮——C-葡萄糖基二氢查尔酮，aspalathin 处理浓度为 75-100μg/ml 也降低了 CRPC 细胞的迁移和侵袭，YAP 的过表达部分挽救了抑制作用。
结论
GRT 通过抑制 YAP 信号和桩蛋白来抑制 CRPC 细胞的迁移和侵袭。
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