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蛋白质组学分析揭示,奥多皂苷 A 通过 ROS-p53 通路诱导结直肠癌细胞 G2/M 期阻滞和凋亡。

Proteomic Analysis Reveals that Odoroside A Triggers G2/M Arrest and Apoptosis in Colorectal Carcinoma Through ROS-p53 Pathway.

机构信息

Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou, 510632, P. R. China.

Institute of Traditional Chinese Medicine Research, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, P. R. China.

出版信息

Proteomics. 2019 Aug;19(15):e1900092. doi: 10.1002/pmic.201900092. Epub 2019 Jul 18.

Abstract

Odoroside A (OA) is an active ingredient extracted from the leaves of Nerium oleander Linn. (Apocynaceae). This study aims to examine the anticancer bioactivity of OA against CRC cells and to investigate the action mechanisms involved. As a result, OA can significantly inhibit cellular ability and induce apoptosis of CRC cells in a concentration-dependent manner without any obvious cytotoxicity in normal colorectal epithelial cells. Then, quantitative proteomics combined with bioinformatics is adopted to investigate the alterations of proteins and signaling pathways in response to OA treatment. As suggested by the proteomic analysis, flow cytometry and Western blotting analyses validate that exposure of CRC cells to OA causes cell cycle arrest and apoptosis, accompanied with the activation of the ROS/p53 signaling pathway. This observation demonstrates that OA, as a natural product, can induce oxidative stress to suppress tumor cell growth, implicating a novel therapeutic agent against CRC without obvious side effects.

摘要

奥多苷 A(OA)是从夹竹桃(夹竹桃科)叶中提取的一种活性成分。本研究旨在研究 OA 对 CRC 细胞的抗癌生物活性,并探讨其作用机制。结果表明,OA 能显著抑制 CRC 细胞的细胞活力,并呈浓度依赖性诱导细胞凋亡,而对正常结直肠上皮细胞无明显细胞毒性。然后,采用定量蛋白质组学结合生物信息学方法研究 OA 处理后蛋白质和信号通路的变化。蛋白质组学分析表明,流式细胞术和 Western blot 分析验证了 OA 处理 CRC 细胞导致细胞周期停滞和细胞凋亡,并激活 ROS/p53 信号通路。这一观察结果表明,OA 作为一种天然产物,可以诱导氧化应激来抑制肿瘤细胞生长,为 CRC 的治疗提供了一种新的治疗药物,且没有明显的副作用。

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