Yuan Sheau-Yun, Cheng Chen-Li, Wang Shian-Shiang, Ho Hao-Chung, Chiu Kun-Yuan, Chen Chuan-Shu, Chen Cheng-Che, Shiau Ming-Yuh, Ou Yen-Chuan
Division of Urology, Department of Surgery, Taichung Veterans General Hospital, Taichung 40705, Taiwan, R.O.C.
Department of Nursing, Hung Kuang University, Taichung 43302, Taiwan, R.O.C.
Oncol Rep. 2017 Feb;37(2):1002-1010. doi: 10.3892/or.2017.5348. Epub 2017 Jan 3.
Escin, a natural pentacyclic triterpenoid compound, exhibits antitumor effects on various types of human cancer cells, but its effect on human renal cancer cells has not been fully elucidated. In the present study, we demonstrated that escin elicits cytotoxic effects on human renal cancer cells (786-O and Caki-1) in a dose-dependent manner, as determined by MTT assay. Escin induced G2/M arrest, and then increased the sub-G1 population, Annexin V binding, activation of caspase-9/-3, cleavage of poly(ADP-ribose) polymerase (PARP) and Bax protein. Escin also decreased the anti-apoptotic protein levels of Bcl-2, X-linked inhibitor of apoptosis protein and survivin. In addition, escin induced reactive oxygen species (ROS) generation, leading to mitochondrial membrane potential dysfunction and inducing apoptosis in 786-O renal cancer cells, which were suppressed by antioxidants, such as NAC. Collectively, our results suggest that escin induces apoptosis via the intrinsic-mitochondrial apoptosis pathway through G2/M arrest and ROS generation in human renal cancer cells. Escin appears to have potential as a clinically useful chemotherapeutic agent for human renal cancer.
七叶皂苷，一种天然的五环三萜类化合物，对多种人类癌细胞具有抗肿瘤作用，但其对人肾癌细胞的作用尚未完全阐明。在本研究中，我们通过MTT法证明七叶皂苷以剂量依赖的方式对人肾癌细胞（786 - O和Caki - 1）产生细胞毒性作用。七叶皂苷诱导G2/M期阻滞，随后增加亚G1期细胞群体、膜联蛋白V结合、半胱天冬酶-9/-3的激活、聚（ADP - 核糖）聚合酶（PARP）的裂解以及Bax蛋白水平。七叶皂苷还降低了抗凋亡蛋白Bcl - 2、X连锁凋亡抑制蛋白和生存素的水平。此外，七叶皂苷诱导活性氧（ROS）生成，导致线粒体膜电位功能障碍并诱导786 - O肾癌细胞凋亡，而抗氧化剂如NAC可抑制这种凋亡。总体而言，我们的数据表明七叶皂苷通过在人肾癌细胞中诱导G2/M期阻滞和ROS生成，经由内源性线粒体凋亡途径诱导凋亡。七叶皂苷似乎有潜力成为一种临床上对人肾癌有用的化疗药物。
