Crocodile choline from Crocodylus siamensis induces apoptosis of human gastric cancer
Crocodile choline from Crocodylus siamensis induces apoptosis of human gastric cancer
复制标题
暹罗鳄鱼胆碱诱导人胃癌细胞凋亡
DOI：
10.1177/1010428317694320
复制
发表时间：
2017-03-28
期刊：
影响因子：
--
通讯作者：
Chen, Qiong-Hua
中科院分区：
文献类型：
--
作者：
Mao, Xiao-Mei;Fu, Qi-Rui;Chen, Qiong-Hua
鳄鱼胆碱是从鳄鱼中分离得到的一种活性化合物，在体内外对人胃癌细胞具有很强的抗癌活性。我们的研究表明，鳄鱼胆碱通过抑制细胞周期蛋白、细胞周期蛋白B1和CDK-1的表达，使细胞周期停滞于G2/M期。此外，鳄鱼胆碱通过线粒体膜电位降低、活性氧产生和Bax/Bcl2比值增加、caspase-3激活和细胞色素c释放而促进线粒体凋亡。此外，本研究首次表明鳄鱼胆碱显著地解除了对Notch途径的调控。鳄鱼胆碱和Notch1短干扰RNA的组合比单独使用任何一种试剂都能显著增加细胞毒性。NOTCH1短干扰RNA敏化并增强鳄鱼胆碱抑制胃癌细胞生长和侵袭的能力。综上所述，这些数据表明鳄鱼胆碱是一种有效的胃癌细胞进展抑制因子，它与线粒体凋亡途径和Notch途径相关。将Notch1抑制剂与鳄鱼胆碱联合使用可能是治疗胃癌的一种新方法。
Crocodile choline, an active compound isolated from Crocodylus siamensis, was found to exert potent anti-cancer activities against human gastric cancer cells in vitro and in vivo. Our study revealed that crocodile choline led to cell cycle arrest at the G2/M phase through attenuating the expressions of cyclins, Cyclin B1, and CDK-1. Furthermore, crocodile choline accelerated apoptosis through the mitochondrial apoptotic pathway with the decrease in mitochondrial membrane potential, the increase in reactive oxygen species production and Bax/Bcl-2 ratio, and the activation of caspase-3 along with the release of cytochrome c. In addition, this study, for the first time, shows that Notch pathway is remarkably deregulated by crocodile choline. The combination of crocodile choline and Notch1 short interfering RNA led to dramatically increased cytotoxicity than observed with either agent alone. Notch1 short interfering RNA sensitized and potentiated the capability of crocodile choline to suppress the cell progression and invasion of gastric cancer. Taken together, these data suggested that crocodile choline was a potent progression inhibitor of gastric cancer cells, which was correlated with mitochondrial apoptotic pathway and Notch pathway. Combining Notch1 inhibitors with crocodile choline might represent a novel approach for gastric cancer.