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从秦皮中获得的生物活性成分会损害FAS和GPI之间的相互作用。

Bioactive ingredients obtained from Cortex Fraxini impair interactions between FAS and GPI.

作者信息

Wu Songtao, Tong Li, Liu Bo, Ai Zhongzhu, Hong Zongchao, You Pengtao, Wu Hezhen, Yang Yanfang

机构信息

Faculty of Pharmacy, Hubei University of Chinese Medicine, Wuhan, 430065, China.

Department of Biochemistry and Molecular Biology, Beijing Normal University, Beijing Key Laboratory, Beijing, 100875, China.

出版信息

Free Radic Biol Med. 2020 May 20;152:504-515. doi: 10.1016/j.freeradbiomed.2019.11.022. Epub 2019 Nov 26.

Abstract

The high expression of fatty acid synthase (FAS) in tumor cells is consistent with their elevated requirement for fatty acids for cell membrane synthesis and energy supply to support their almost unlimited proliferation. The expression levels of FAS in tumor cells are related to their proliferation, invasion, and metastasis. This study investigated the possible bioactive ingredients (fraxin, esculetin, scopolin et al.) of Cortex Fraxini and their effects on the interaction between specific proteins. We used microscale thermophoresis (MST) to show that our target protein, FAS (screened by combining transcriptome and network pharmacology), bound to the active compounds in Cortex Fraxini. It was found that FAS bound strongly to Glucose-6-phosphate isomerase (GPI), and that scopolin could affect this interaction by proteomics and MST. The results of this study demonstrate that the active compounds in Cortex Fraxini could play an anti-tumor role by binding to FAS and inhibiting the interactions between FAS and GPI to affect glucose and lipid metabolism, and that the protein pathway is a potential novel target for tumor treatment.

摘要

脂肪酸合酶(FAS)在肿瘤细胞中的高表达与其对脂肪酸的需求增加相一致,这些脂肪酸用于细胞膜合成和能量供应,以支持其几乎不受限制的增殖。肿瘤细胞中FAS的表达水平与其增殖、侵袭和转移有关。本研究调查了秦皮的可能生物活性成分(秦皮苷、七叶亭、秦皮甲素等)及其对特定蛋白质之间相互作用的影响。我们使用微量热泳动(MST)表明,我们的靶蛋白FAS(通过转录组和网络药理学相结合筛选)与秦皮中的活性化合物结合。研究发现,FAS与葡萄糖-6-磷酸异构酶(GPI)强烈结合,并且秦皮甲素可以通过蛋白质组学和MST影响这种相互作用。本研究结果表明,秦皮中的活性化合物可通过与FAS结合并抑制FAS与GPI之间的相互作用来影响葡萄糖和脂质代谢,从而发挥抗肿瘤作用,并且该蛋白质途径是肿瘤治疗的潜在新靶点。

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