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, China.
Food Funct. 2018 Nov 14;9(11):5536-5546. doi: 10.1039/c8fo01137k.
Colorectal cancer (CRC) is one of the most common cancers worldwide with poor survival and limited therapeutic options, and there is an urgent need to develop novel therapeutic agents with good treatment efficiency and low toxicity. This study aims to examine the anticancer bioactivity of liensinine, a constituent of Nelumbo nucifera Gaertn, in CRC and investigate the action mechanisms involved.
Liensinine was found to induce apoptosis and exert a significant inhibitory effect on the proliferation and colony-forming ability of CRC cells in a dose-dependent manner without any observed cytotoxicity on normal colorectal epithelial cells. Mechanistically, our data from quantitative proteomics, western blot analysis and flow cytometry analyses demonstrated that exposure of CRC cells to liensinine caused cell cycle arrest, mitochondrial dysfunction and apoptosis, accompanied by the activation of the JNK signaling pathway. Furthermore, animal experiments showed that liensinine markedly suppressed the growth of CRC tumor xenografts in nude mice by reducing the Ki-67 proliferation index, but did not damage the vital organs of the animals.
This study demonstrated for the first time that liensinine, a food-source natural product, could be a novel therapeutic strategy for treating CRC without obvious side effects.
结直肠癌（CRC）是全球最常见的癌症之一，其生存率低，治疗选择有限，因此迫切需要开发具有良好治疗效果和低毒性的新型治疗药物。本研究旨在研究莲子心碱（Nelumbo nucifera Gaertn 的一种成分）在 CRC 中的抗癌生物活性，并探讨其作用机制。
研究发现，莲子心碱能够诱导细胞凋亡，并在剂量依赖性方式下显著抑制 CRC 细胞的增殖和集落形成能力，而对正常结直肠上皮细胞无细胞毒性。从定量蛋白质组学、Western blot 分析和流式细胞术分析中我们获得的机制数据表明，暴露于莲子心碱会导致 CRC 细胞周期停滞、线粒体功能障碍和细胞凋亡，并激活 JNK 信号通路。此外，动物实验表明，莲子心碱通过降低 Ki-67 增殖指数显著抑制裸鼠 CRC 肿瘤异种移植物的生长，但对动物的重要器官没有损伤。
本研究首次表明，莲子心碱作为一种食物源天然产物，可能是一种治疗 CRC 的新型治疗策略，且无明显副作用。
