title: Identification of the anti-tumor activity and mechanisms of nuciferine through a network pharmacology approach.
abstract: OBJECTIVE
  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 SY5Y 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.
  
  
  CONCLUSIONS
  By using a TCM network pharmacology method, nuciferine is identified as an anti-tumor agent against human neuroblastoma and mouse colorectal cancer in vitro and in vivo, through inhibiting the PI3K-AKT signaling pathways and IL-1 levels.
authors.affiliation: Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China.|MOE Key Lab of Bioinformatics, Bioinformatics Division, TNLIST and Department of Automation, Tsinghua University, Beijing 100084, China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Qi
authors.affiliation: Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China.|MOE Key Lab of Bioinformatics, Bioinformatics Division, TNLIST and Department of Automation, Tsinghua University, Beijing 100084, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.affiliation: MOE Key Lab of Bioinformatics, Bioinformatics Division, TNLIST and Department of Automation, Tsinghua University, Beijing 100084, China.
authors.forename: Hui-Ying
authors.initials: HY
authors.lastname: Li
authors.affiliation: Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China.
authors.forename: Yu-Bing
authors.initials: YB
authors.lastname: Cao
authors.affiliation: MOE Key Lab of Bioinformatics, Bioinformatics Division, TNLIST and Department of Automation, Tsinghua University, Beijing 100084, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Bai
authors.affiliation: The Second Hospital Affiliated to Tianjin University of Traditional Chinese Medicine, Tianjin 300150, China.
authors.forename: Xiao-Jing
authors.initials: XJ
authors.lastname: Fan
authors.affiliation: Tianjin International Joint Academy of Biotechnology & Medicine, Tianjin 300457, China.
authors.forename: Shu-Yan
authors.initials: SY
authors.lastname: Wang
authors.affiliation: MOE Key Lab of Bioinformatics, Bioinformatics Division, TNLIST and Department of Automation, Tsinghua University, Beijing 100084, China.|Tianjin International Joint Academy of Biotechnology & Medicine, Tianjin 300457, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.affiliation: MOE Key Lab of Bioinformatics, Bioinformatics Division, TNLIST and Department of Automation, Tsinghua University, Beijing 100084, China.
authors.forename: Shao
authors.initials: S
authors.lastname: Li
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001060:Aporphines / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D058534:Class I Phosphatidylinositol 3-Kinases; D016000:Cluster Analysis; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D001060:Aporphines; D058534:Class I Phosphatidylinositol 3-Kinases; D004365:Drugs, Chinese Herbal; D019869:Phosphatidylinositol 3-Kinases; C421683:Pik3cd protein, mouse; C008692:nuciferine