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Aspalathin-rich green Aspalathus linearis extract suppresses migration and invasion of human castration-resistant prostate cancer cells via inhibition of YAP signaling.
Phytomedicine ( IF 6.7 ) Pub Date : 2020-03-18 , DOI: 10.1016/j.phymed.2020.153210
Shih-Han Huang , Yung-Hsi Kao , Christo J.F. Muller , Elizabeth Joubert , Chih-Pin Chuu

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.

中文翻译:

富含Aspalathin的绿色Aspalathus linearis提取物通过抑制YAP信号传导来抑制人类去势抵抗性前列腺癌细胞的迁移和侵袭。

背景技术超过80%的晚期前列腺癌(PCa)病例发生骨转移,其5年生存率达到25%。先前,我们报道了GRT是一种标准化的,药用级富含石笋的提取物(12.78 g阿斯帕辛/ 100 g提取物),它是由线性天麻叶片和细茎产生的绿色如意宝制成的,可抑制PCa细胞的增殖,值得这项研究旨在确定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类CRPC细胞的迁移和侵袭。方法采用Transwell法检测GRT对CRPC细胞迁移和侵袭的影响。进行了Micro-Western Array(MWA)和Western印迹分析以揭示潜在的分子机制。结果用25-100μg/ ml 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处理可抑制yes相关蛋白(YAP),刺激巨噬细胞1蛋白(MST1),phospho-MST1 / phospho-MST2 T183 / T180和paxillin的蛋白水平,但增加E的丰度-钙黏着蛋白。YAP的过表达挽救了GRT对CRPC细胞迁移和侵袭的抑制作用。浓度为75-100μg/ ml的GRT主要类黄酮-C-葡萄糖基二氢查耳酮,阿斯帕拉丁-的处理也减少了CRPC细胞的迁移和侵袭,并且通过YAP的过表达部分缓解了抑制作用。
更新日期:2020-03-19
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