民族民间药用植物吉祥草中基于线粒体途径诱导CASKI细胞凋亡活性皂苷的成分解析及其抗肿瘤作用机制研究

项目名称： 民族民间药用植物吉祥草中基于线粒体途径诱导CASKI细胞凋亡活性皂苷的成分解析及其抗肿瘤作用机制研究

项目编号： No.21272136

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 数理科学和化学

项目作者： 邹坤

作者单位： 三峡大学

项目金额： 80万元

中文摘要： 吉祥草(Reineckia carnea)为百合科铃兰族吉祥草属草本植物，药用全草，在我国黄河以南地区广泛分布，资源十分丰富，是土家族和苗族等民族的名药，在湖北、云南等省已收载为地方中药材。在我们的前期研究中发现，吉祥草总皂苷含有结构丰富的甾体皂苷，具有良好的CASKI细胞毒活性，对正常细胞毒性很小，对肿瘤细胞具有一定的选择性，其中一个含量较高的螺甾皂苷IC50为3.71微摩，可显著诱导CASKI细胞凋亡，阻滞细胞增殖于G2/M期，伴随细胞色素C大量释放。已有研究表明，线粒体途径的化疗药物在解决肿瘤耐药性方面具有独特优势,且线粒体瓦解与肿瘤细胞衰老直接相关。本课题旨在系统分离纯化吉祥草总皂苷、以其诱导细胞凋亡作用的线粒体途径为立论基础探讨其作用机制，以期发现结构新颖、主要经由线粒体途径作用的抗肿瘤先导化合物。

中文关键词： 吉祥草；甾体皂苷；全合成；抗肿瘤；作用机制

英文摘要： Reineckia carnea belongs to Reineckia species of Convallariaceae in Liliaceae family, which is abundant in the region of the south of the Yellow rivor in China. As a folk and enthanic medicine, its total plant was specified in local pharmacopoeia of Hubei Province and Yunnan Province, and reputed in Tujia and Miao Nations. Our previous study showed that it contained enriched steroidal saponins in structures and content, potent citotoxicity against CASKI tumor cell line, little toxicity towards normal cells, and selected inhibitory action towards tumor cells. Also, a sapinin abounded in this plant exerted strong inhibitory activity towards CASKI cells with its IC50 as 3.71 micromole. Meanwhile, this saponin markedly inhibited apoptosis of CASKI cells and arrested the cell proliferation to G2/M stage, accompanied with the massive release of cytochrome C. It was reported that chemotherapeutics via mitochondria showed many characteristic advantages, such as age-promoting for tumor cells and anti-resistance for chemotherapeutics. Significantly, this kind of steroidal saponin is possibbly involved in these events above. This program intends to explore the induction mechanism of CASKI cell apoptosis via mitochondria by steroidal saponins, based on systematically isolated and elucidated the steroidal saponins in Reineck

英文关键词： Reineckia carnea；steroidal saponins；total synthesis；antitumor activity；mechanism of action