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Natural cordycepin induces apoptosis and suppresses metastasis in breast cancer cells by inhibiting the Hedgehog pathway
Food & Function ( IF 5.1 ) Pub Date : 2020/03/11 , DOI: 10.1039/c9fo02879j
Chengyi Liu 1, 2, 3, 4, 5 , Meng Qi 1, 2, 3, 4, 5 , Lin Li 1, 2, 3, 4, 5 , Yuan Yuan 1, 2, 3, 4, 5 , Xiaoping Wu 1, 2, 3, 4, 5 , Junsheng Fu 1, 2, 3, 4, 5
Affiliation  

In the study, we investigated the role of the hedgehog (Hh) pathway in cordycepin's effects on human breast cancer cells, with respect to cell growth, apoptosis and metastasis. We found cordycepin to have low toxicity but significant anticancer effects. Cordycepin-induced apoptosis led to increased PUMA, CYTO-C, FAS, DR4/5, and cleaved caspase-3; and decreased BCL-2, XIAP and PDGFR-α. Cordycepin inhibited metastasis, which was associated with up-regulated E-cadherin, and down-regulated N-cadherin, SNAIL, SLUG and ZEB1. Cordycepin also inhibited expression of Hh pathway components and GLI transcriptional activity. Inversely, knockout of GLI blocked cordycepin-mediated effects on the apoptotic, epithelial–mesenchymal transition (EMT) and Notch pathways, which indicates that GLI is crucial for cordycepin's effects against breast cancer. Inhibition of GLI enhanced cordycepin's effect on breast cancer cell growth. To our knowledge, this is the first study of cordycepin's effect on the Hh pathway in breast cancer, and provides preliminary data for the in vivo study, and possible therapeutic use, of cordycepin.

中文翻译:

天然虫草素通过抑制Hedgehog途径诱导凋亡并抑制乳腺癌细胞的转移

在这项研究中,我们研究了刺猬(Hh)通路在虫草素对人乳腺癌细胞的影响方面的作用,涉及细胞生长,凋亡和转移。我们发现虫草素毒性低,但具有明显的抗癌作用。虫草素诱导的细胞凋亡导致PUMA,CYTO-C,FAS,DR4 / 5和caspase-3的裂解增加。BCL-2,XIAP和PDGFR-α降低。虫草素抑制转移,将其用上调的相关联的E-钙粘蛋白,和下调N-钙粘蛋白SNAILSLUGZEB1。虫草素还抑制Hh通路成分的表达和GLI转录活性。相反,敲除GLI阻断了虫草素介导的对细胞凋亡,上皮-间质转化(EMT)和Notch途径的影响,这表明GLI对于虫草素对乳腺癌的作用至关重要。抑制GLI增强了虫草素对乳腺癌细胞生长的作用。据我们所知,这是虫草素对乳腺癌Hh途径的作用的首次研究,并为虫草素的体内研究和可能的治疗用途提供了初步数据。
更新日期:2020-03-27
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