文章摘要
柳珊瑚来源的愈创木薁倍半萜生物碱化合物Muriceidine A体外抗肿瘤活性的研究
Anti-tumor activity in vitro of a novel guaiazulene sesquiterpene alkaloid Muriceidine A from the gorgonian Muriceides collaris
投稿时间:2018-12-07  修订日期:2019-01-09
DOI:
中文关键词: Muriceidine A  HeLa细胞  增殖抑制  周期阻滞  凋亡诱导
英文关键词: Muriceidine A  HeLa cells  proliferation inhibition  cycle arrest  apoptosis
基金项目:国家自然科学基金(NO.81673450),NSFC-山东省联合基金(U1606403), 青岛海洋科学与技术国家实验室鳌山科技创新计划项目(No.2015ASKJ02)
作者单位E-mail
买小圆 中国海洋大学 海洋国家实验室海洋药物与生物制品功能实验室 may_be_guu@163.com 
唐薇 中国海洋大学 海洋国家实验室海洋药物与生物制品功能实验室  
戚欣 中国海洋大学 海洋国家实验室海洋药物与生物制品功能实验室  
李国强 中国海洋大学医药学院海洋药物教育部重点实验室  
李静 中国海洋大学 海洋国家实验室海洋药物与生物制品功能实验室 ljlilac@163.com 
刘在亮 中国海洋大学 海洋国家实验室海洋药物与生物制品功能实验室  
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中文摘要:
      目的 对从高领类尖柳珊瑚Muriceides collaris中分离得到的1种愈创木薁倍半萜生物碱Muriceidine A进行体外抗肿瘤活性研究。方法 MTT法测定Muriceidine A对多种肿瘤细胞株的增殖抑制作用。流式细胞仪检测Muriceidine A对HeLa细胞周期及凋亡的影响。Western Blot检测Muriceidine A对HeLa细胞中周期相关蛋白、凋亡相关蛋白、E6/E7蛋白及其下游信号分子的影响。结果 Muriceidine A体外对多种肿瘤细胞均有增殖抑制作用,其中对HeLa 细胞的抑制作用最强,IC50为17.40 μmol/L。流式细胞仪分析及Western Blot检测显示,Muriceidine A 能够以剂量依赖性的方式使HeLa细胞阻滞在G2/M期,可通过激活Caspase依赖的线粒体凋亡途径诱导HeLa细胞凋亡。同时,Western Blot检测显示Muriceidine A能够通过降低HeLa细胞中E6/E7的水平,抑制ERK和STAT3的磷酸化。结论 Muriceidine A体外对人宫颈腺癌细胞HeLa具有较强的细胞毒作用。本研究为该小分子化合物今后的合成与改造提供思路与方向。
英文摘要:
      Objective To investigated the anti-tumor activity in vitro of a novel compound Muriceidine A, which is a novel guaiazulene sesquiterpene alkaloid isolated from the gorgonian Muriceides collaris. Methods MTT assay was used to determine the proliferation inhibition effect of Muriceidine A on various tumor cells. Flow cytometry was used to detect the effect of Muriceidine A on HeLa cell cycle and apoptosis. The effects of Muriceidine A on cycle-associated proteins, apoptosis-related proteins, E6/E7 proteins and downstream signaling molecules in HeLa cells were assessed by Western Blot. Results Muriceidine A inhibited the proliferation of various tumor cells in vitro, and the inhibitory effect on human cervical cancer cell HeLa was the strongest, with an IC50 of 17.40 μmol/L. Flow cytometry analysis and Western Blot assay showed that Muriceidine A could arrest HeLa cells in G2/M phase in a dose-dependent manner, and induce HeLa cell apoptosis by activating Caspase-dependent mitochondrial apoptosis pathway. Meanwhile, Western Blot assay showed that Muriceidine A inhibited the phosphorylation of ERK and STAT3 by reducing the level of E6/E7 in HeLa cells. Conclusion Muriceidine A had a strong cytotoxic effect on human cervical cancer cell line HeLa in vitro. The anti-tumor activity in vitro of Muriceidine A provided new ideas and directions for the future synthesis and transformation of it.
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