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Uncovering the anti-proliferation mechanism and bioactive compounds in red kidney bean coat against B16-F10 melanoma cells by metabolomics and network pharmacology analysis†
Food & Function ( IF 6.1 ) Pub Date : 2019-01-15 00:00:00 , DOI: 10.1039/c8fo01738g
Jia-Hui Nie 1, 2, 3, 4, 5 , Jian-Xiang Huang 3, 4, 6 , Qing-Rong Wu 3, 4, 6 , Xue-Mei Qin 1, 2, 3, 4 , Zhen-Yu Li 1, 2, 3, 4
Affiliation  

In this study, coat (RKBC) and kernel (RKBK) extracts of red kidney bean were prepared, and their chemical compositions and potential anti-cancer activity against B16-F10 cells were evaluated. Then the anti-proliferation mechanisms of the active RKBC extract were investigated by flow cytometry analysis, cellular metabolomics, network pharmacology and western blotting. The RKBC extract inhibited B16-F10 cell proliferation and migration in a dose-dependent manner. Further analysis showed that RKBC induced G1 and G2/M phase arrest, and triggered apoptosis and vacuolization. Mechanistically, RKBC significantly increased the cellular content of cGMP, decreased the levels of AKT1/2/3 and cleaved-MMP2, and up-regulated the expression of Bcl-xl. Besides, network pharmacology revealed that RKBC potentially influenced the cell cycle via the regulation of CDK2 and CDK4. Finally, quercetin might serve as the major active component in the RKBC extract. In conclusion, our study showed the potential of the RKBC extract for the prevention or treatment of melanoma.

中文翻译:

通过代谢组学和网络药理学分析发现红芸豆皮中抗B16-F10黑色素瘤细胞的抗增殖机制和生物活性化合物

在这项研究中,制备了红芸豆的外皮(RKBC)和核仁(RKBK)提取物,并评估了它们的化学组成和对B16-F10细胞的潜在抗癌活性。然后通过流式细胞仪分析,细胞代谢组学,网络药理学和蛋白质印迹研究了活性RKBC提取物的抗增殖机制。RKBC提取物以剂量依赖的方式抑制B16-F10细胞的增殖和迁移。进一步的分析表明,RKBC诱导了G1和G2 / M期的阻滞,并引发了细胞凋亡和空泡化。从机理上讲,RKBC显着增加了cGMP的细胞含量,降低了AKT1 / 2/3和裂解的MMP2的水平,并上调了Bcl-xl的表达。此外,网络药理学发现RKBC可能影响细胞周期通过CDK2和CDK4的调节。最后,槲皮素可能是RKBC提取物中的主要活性成分。总之,我们的研究表明RKBC提取物具有预防或治疗黑色素瘤的潜力。
更新日期:2019-01-15
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