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从款冬花多糖中合成银纳米粒子及其基于细胞代谢组学方法揭示其抗癌机制

Synthesis of Silver Nanoparticles from the Polysaccharide of Farfarae Flos and Uncovering Its Anticancer Mechanism Based on the Cell Metabolomic Approach.

机构信息

Modern Research Center for Traditional Chinese Medicine, the Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, Taiyuan 030006, China.

出版信息

J Proteome Res. 2022 Jan 7;21(1):172-181. doi: 10.1021/acs.jproteome.1c00668. Epub 2021 Dec 7.

Abstract

In this study, the polysaccharide of Farfarae Flos (FFP) was utilized as a reducing agent to the green synthesis of FFP@AgNPs, and the anticancer activity was evaluated using the HT29 cells. The results showed that the FFP@AgNPs could significantly decrease proliferation ability, inhibit migration, and promote cell apoptosis of HT29 cells, which suggested that the FFP@AgNPs showed significant, strong cytotoxicity against HT29 cells. The cell metabolomic analysis coupled with the heatmap showed an obvious metabolome difference for the cells with and without FFP@AgNPs treatment, which was related to 51 differential metabolites. Four metabolic pathways were determined as the key pathways, and the representative functional metabolites and metabolic pathways were validated . Nicotinic acid (NA) was revealed as the key metabolite relating with the effect of FFP@AgNPs, and it was interesting that NA supplementation could inhibit the proliferation ability of HT29 cells , lead to mitochondrial dysfunction, reduce intracellular ATP, and damage the integrity of the cell membrane, which exhibited a similar effect as FFP@AgNPs. In conclusion, this study not only revealed the anticancer mechanism of FFP@AgNPs against the HT29 cells but also provided the important reference that NA shows a potential role in the development of a therapy for colorectal cancer.

摘要

在这项研究中,我们利用款冬花多糖(FFP)作为还原剂,成功绿色合成了 FFP@AgNPs,并通过 HT29 细胞评估了其抗癌活性。结果表明,FFP@AgNPs 可显著降低 HT29 细胞的增殖能力,抑制迁移,并促进细胞凋亡,表明 FFP@AgNPs 对 HT29 细胞具有显著、强烈的细胞毒性。细胞代谢组学分析结合热图显示,FFP@AgNPs 处理前后细胞的代谢组存在明显差异,涉及 51 个差异代谢物。确定了四个关键代谢途径,验证了代表性的功能代谢物和代谢途径。烟酰胺(NA)被揭示为与 FFP@AgNPs 作用相关的关键代谢物,有趣的是,NA 补充可抑制 HT29 细胞的增殖能力,导致线粒体功能障碍,降低细胞内 ATP 水平,并破坏细胞膜完整性,这与 FFP@AgNPs 的作用相似。总之,本研究不仅揭示了 FFP@AgNPs 抑制 HT29 细胞的抗癌机制,还提供了重要的参考,即 NA 在开发结直肠癌治疗方法方面具有潜在作用。

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