Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, Jiangsu Province, People's Republic of China.
Department of Ophthalmology, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi 214023, Jiangsu Province, People's Republic of China.
J Biochem Mol Toxicol. 2018 Jan;32(1). doi: 10.1002/jbt.22001. Epub 2017 Sep 28.
Ziyuglycoside I (Ziyu I), one of the major components isolated from the root of Sanguisorba officinalis L., has been proved for the antitumor properties on oral cancer, prostate cancer, and colorectal cancer. However, the effect of Ziyu I on retinoblastoma (RB) is not well understood. In this study, we investigated the inhibitory effect and underlying molecular mechanism of Ziyu I on human RB WERI-Rb-1 cells. Our results indicated that Ziyu I could suppress cell viability and induce mitochondrial-dependent cell apoptosis in WERI-Rb-1 cells. Furthermore, Ziyu I treatment increased p53 expression as well as improved p53 stabilization through downregulation of pS166-Mdm2 and upregulation of phosphorylated- and acetylated-p53. Blockade of p53 significantly attenuated Ziyu I-induced mitochondrial dysfunction. Our findings demonstrate that Ziyu I exhibits excellent anticancer effect on human RB WERI-Rb-1 cells by triggering p53 activation, and imply Ziyu I as a potential compound for chemotherapy of human RB.
梓醇苷 I（Ziyu I）是从苦菜根中分离得到的主要成分之一，已被证明具有抗肿瘤作用，可用于治疗口腔癌、前列腺癌和结直肠癌。然而，梓醇苷 I 对视网膜母细胞瘤（RB）的作用尚不清楚。在这项研究中，我们研究了梓醇苷 I 对人 RB WERI-Rb-1 细胞的抑制作用及其潜在的分子机制。结果表明，梓醇苷 I 可抑制 WERI-Rb-1 细胞的活力并诱导其线粒体依赖性细胞凋亡。此外，梓醇苷 I 处理通过下调 pS166-Mdm2 和上调磷酸化和乙酰化 p53 来增加 p53 的表达并改善 p53 的稳定性。p53 阻断显著减弱了梓醇苷 I 诱导的线粒体功能障碍。我们的研究结果表明，梓醇苷 I 通过触发 p53 激活对人 RB WERI-Rb-1 细胞表现出良好的抗癌作用，提示梓醇苷 I 可能成为治疗人类 RB 的潜在化疗药物。
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