管托皂苷 I 诱导 EC109 细胞死亡涉及内在凋亡途径和 G2/M 细胞周期阻滞。
Intrinsic apoptotic pathway and G2/M cell cycle arrest involved in tubeimoside I-induced EC109 cell death.
机构信息
School of Pharmaceutical Sciences, Xiamen University, Xiamen 361005, China.
出版信息
Chin J Cancer Res. 2013 Jun;25(3):312-21. doi: 10.3978/j.issn.1000-9604.2013.06.03.
Abstract
OBJECTIVE
Squamous esophageal carcinoma is highly prevalent in developing countries, especially in China. Tu Bei Mu (TBM), a traditional folk medicine, has been used to treat esophageal squamous cell carcinoma (ESCC) for a long term. tubeimoside I (TBMS1) is the main component of TBM, exhibiting great anticancer potential. In this study, we investigated the mechanism of TBMS1 cytotoxic effect on EC109 cells.
METHODS
Comparative nuclear proteomic approach was applied in the current study and we identified several altered protein spots. Further biochemical studies were carried out to detect the mitochondrial membrane potential, cell cycle and corresponding proteins' expression and location.
RESULTS
Subcellular proteomic study in the nucleus from EC109 cells revealed that altered proteins were associated with mitochondrial function and cell proliferation. Further biochemical studies showed that TBMS1-induced molecular events were related to mitochondria-induced intrinsic apoptosis and P21-cyclin B1/cdc2 complex-related G2/M cell cycle arrest.
CONCLUSIONS
Considering the conventional application of TBM in esophageal cancer, TBMS1 therefore may have a great potential as a chemotherapeutic drug candidate for ESCC.
摘要
目的
鳞状食管癌在发展中国家高发，尤以中国为甚。土贝母（TBM）是一种传统民间药物，长期以来一直被用于治疗食管鳞状细胞癌（ESCC）。土贝母苷甲（TBMS1）是 TBM 的主要成分，具有很强的抗癌潜力。在本研究中，我们研究了 TBMS1 对 EC109 细胞的细胞毒性作用的机制。
方法
本研究采用比较核蛋白质组学方法，鉴定了几个差异表达的蛋白点。进一步的生化研究检测了线粒体膜电位、细胞周期及相应蛋白的表达和定位。
结果
EC109 细胞核的亚细胞蛋白质组学研究表明，改变的蛋白与线粒体功能和细胞增殖有关。进一步的生化研究表明，TBMS1 诱导的分子事件与线粒体诱导的内在细胞凋亡和 P21-cyclin B1/cdc2 复合物相关的 G2/M 细胞周期阻滞有关。
结论
鉴于 TBM 在食管癌中的传统应用，TBMS1 可能具有作为 ESCC 化疗药物候选物的巨大潜力。
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