牛蒡子苷元衍生物对肿瘤细胞的抑制作用及其机制研究
Inhibitory Effect of Arctigenin Derivatives on Tumor Cells and Its Mechanism
刘芳菲 1舒晖 1刘丁瑞 1张欣宏 1朱颜铂 2赵岩 1蔡恩博 1韩佳宏1
作者信息
- 1. 吉林农业大学中药材学院,长春 130118
- 2. 吉林大学第一医院干细胞与肿瘤中心器官再生与移植教育部重点实验室,长春 130021
- 折叠
摘要
在该研究中,共设计出27种牛蒡子苷元衍生物,其中9种为新型靶向肿瘤细胞线粒体的衍生物.生物学研究表明,与牛蒡子苷元相比,所有连接有三苯基膦的化合物的抗肿瘤活性均有大幅度的提高.其中,Mito-ARG-7对A549细胞显示出高度的选择性,其抗肿瘤活性相对于牛蒡子苷元增加了 86.38％.其研究表明,Mito-ARG-7的抗肿瘤机制包括明显增加A549细胞内活性氧的产生量,引起细胞线粒体膜电位下降,促进内源性线粒体凋亡信号通路上的凋亡蛋白Cytochrome C自线粒体向细胞质的释放,以及引起Caspase家族蛋白的活化,最终诱发肿瘤细胞的凋亡.该研究合成的具有线粒体靶向功能的新型牛蒡子苷元衍生物为靶向抗肿瘤药物的研发提供了参考.
Abstract
In this study,a total of 27 ARG(arctigenin)derivatives were designed,of which nine were novel deriv-atives targeting tumor cell mitochondria.Biological studies showed that all the triphenylphosphine conjugated compounds had a significant increase in anti-tumor activity compared with ARG.Among them,Mito-ARG-7 showed a high selectivity against A549 cells,and its anti-tumor activity was increased by 86.38％compared with ARG.This study showed that the anti-tumor mechanisms of Mito-ARG-7 included significantly increasing the production of reactive oxygen species in A549 cells,causing a decrease in mitochondrial membrane potential,promoting the release of apoptotic protein Cytochrome C from mitochondria to cytoplasm in the endogenous mitochondrial apoptosis signaling pathway,and causing the activation of Caspase family proteins to eventually induce the apoptosis of tumor cells.The novel arctigenin derivative with mito-chondrial targeting function synthesized in this study provides a reference for the development of targeted anti-tumor drugs.
关键词
牛蒡子苷元衍生物/A549细胞/线粒体途径/细胞凋亡Key words
arctigenin derivatives/A549 cells/mitochondrial pathway/apoptosis引用本文复制引用
基金项目
吉林省科技发展计划(20210101234JC)
出版年
2024
NETL
NSTL
万方数据