Inhibition of Gli/hedgehog signaling in prostate cancer cells by "cancer bush" Sutherlandia frutescens extract.
Inhibition of Gli/hedgehog signaling in prostate cancer cells by "cancer bush" Sutherlandia frutescens extract.
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“癌丛”Sutherlandia frutescens 提取物抑制前列腺癌细胞中的 Gli/hedgehog 信号传导。
DOI：
10.1002/cbin.10544
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发表时间：
2016
影响因子：
3.9
通讯作者：
Lubahn,DennisB
中科院分区：
文献类型：
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作者：
Lin,Hui;Jackson,GlennA;Lu,Yuan;Drenkhahn,SaraK;Brownstein,KoreyJ;Starkey,NicholasJ;Lamberson,WilliamR;Fritsche,KevinL;Mossine,ValeriV;Besch-Williford,CynthiaL;Folk,WilliamR;Zhang,Yong;Lubahn,DennisB
Sutherlandia frutescensis是一种药用植物，传统上用于治疗各种类型的人类疾病，包括癌症。先前对几种植物的研究将前列腺癌生长的抑制与Gli/Hedgehog（Gli/Hh）信号通路的抑制联系起来。在这里，我们假设S. frutescens与其在前列腺癌中抑制Gli/Hh信号有关。我们发现，S处理的人前列腺癌细胞PC 3和LNCaP以及小鼠前列腺癌细胞TRAMP-C2具有剂量和时间依赖性生长抑制作用。Frutescens甲醇提取物（SLE）。我们还观察到用SLE处理的Shh Light II和TRAMP-C2 QGli细胞中Gli报告基因活性的剂量依赖性抑制。此外，SLE可以通过在Gli/Hh信号激动剂（SAG）存在下阻断Gli 1和Ptched 1基因表达来抑制Gli/Hh信号传导。日粮中添加S. frutescens抑制TRAMP小鼠前列腺低分化癌的形成。最后，我们发现Sutherlandioside D是粗提物中最有效的化合物，可以抑制Shh Light II细胞中的Gli报告基因。总之，这表明S.结果表明，紫云英提取物可能通过靶向Gli/Hh信号通路发挥抗肿瘤作用，其中Sutherlandioside D是活性化合物之一。
Sutherlandia frutescensis a medicinal plant, traditionally used to treat various types of human diseases, including cancer. Previous studies of several botanicals link suppression of prostate cancer growth with inhibition of the Gli/hedgehog (Gli/Hh) signaling pathway. Here we hypothesized the anti‐cancer effect ofS. frutescenswas linked to its inhibition of the Gli/Hh signaling in prostate cancer. We found a dose‐ and time‐dependent growth inhibition in human prostate cancer cells, PC3 and LNCaP, and mouse prostate cancer cell, TRAMP‐C2, treated withS. frutescensmethanol extract (SLE). We also observed a dose‐dependent inhibition of the Gli‐reporter activity in Shh Light II and TRAMP‐C2QGli cells treated with SLE. In addition, SLE can inhibit Gli/Hh signaling by blocking Gli1 and Ptched1 gene expression in the presence of a Gli/Hh signaling agonist (SAG). A diet supplemented withS. frutescenssuppressed the formation of poorly differentiated carcinoma in prostates of TRAMP mice. Finally, we found Sutherlandioside D was the most potent compound in the crude extract that could suppress Gli‐reporter in Shh Light II cells. Together, this suggests that theS. frutescensextract may exert anti‐cancer effect by targeting Gli/Hh signaling, and Sutherlandioside D is one of the active compounds.