Identification of the anti-tumor activity and mechanisms of nuciferine through a network pharmacology approach

• Published in: Acta pharmacologica Sinica Vol. 37; no. 7; pp. 963 - 972
• Main Authors: Qi, Quan, Li, Rui, Li, Hui-ying, Cao, Yu-bing, Bai, Ming, Fan, Xiao-jing, Wang, Shu-yan, Zhang, Bo, Li, Shao
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.07.2016; Nature Publishing Group
• Subjects: Animals; Antineoplastic Agents - pharmacology; Aporphines - pharmacology; Biomedical and Life Sciences; Biomedicine; Cell Line, Tumor; Cell Survival - drug effects; Cluster Analysis; Drugs, Chinese Herbal - pharmacology; Humans; Immunology; Internal Medicine; Medical Microbiology; Mice; Mice, Nude; Neoplasm Invasiveness; Original; original-article; Pharmacology/Toxicology; Phosphatidylinositol 3-Kinases - metabolism; Signal Transduction - drug effects; Vaccine; Xenograft Model Antitumor Assays; 医药网络; 抗肿瘤活性; 机制; 活性鉴定; 生物碱; 神经母细胞瘤; 药理学; 荷叶; nuciferine; colorectal cancer; IL-1; neuroblastoma; drugCIPHER; TCM network pharmacology; anti-tumor agent; PI3K-AKT
• ISSN: 1671-4083; 1745-7254; 1745-7254
• DOI: 10.1038/aps.2016.53

Aim： Nuciferine is an aporphine alkaloid extracted from lotus leaves, which is a raw material in Chinese medicinal herb for weight loss. In this study we used a network pharmacology approach to identify the anti-tumor activity of nuciferine and the underlying mechanisms. Methods： The pharmacological activities and mechanisms of nuciferine were identified through target profile prediction, clustering analysis and functional enrichment analysis using our traditional Chinese medicine （TCM） network pharmacology platform. The anti- tumor activity of nuciferine was validated by in vitro and in vivo experiments. The anti-tumor mechanisms of nuciferine were predicted through network target analysis and verified by in vitro experiments. Results： The nuciferine target profile was enriched with signaling pathways and biological functions, including ＂regulation of lipase activity＂, ＂response to nicotine＂ and ＂regulation of cell proliferation＂. Target profile clustering results suggested that nuciferine to exert anti-tumor effect. In experimental validation, nuciferine （0.8 mg/mL） markedly inhibited the viability of human neuroblastoma SY5Y cells and mouse colorectal cancer CT26 cells in vitro, and nuciferine （0.05 mg/mL） significantly suppressed the invasion of 6 cancer cell lines in vitro. Intraperitoneal injection of nuciferine （9.5 mg/mL, ip, 3 times a week for 3 weeks） significantly decreased the weight of SYSY and CT26 tumor xenografts in nude mice. Network target analysis and experimental validation in SY5Y and CT26 cells showed that the anti-tumor effect of nuciferine was mediated through inhibiting the PI3K-AKT signaling pathway and IL-1 levels in SY5Y and CT26 cells. Conclusion： By using a TCM network pharmacology method, nuciferine is neuroblastoma and mouse colorectal cancer in vitro and in vivo, through dentified as an anti-tumor agent against human nhibiting the PI3K-AKT signaling pathways and IL-1 levels