PUBLICATION

1-Methoxycarbony-β-carboline from Picrasma quassioides exerts anti-angiogenic properties in HUVECs in vitro and zebrafish embryos in vivo

Authors
Lin, Q.H., Qu, W., Xu, J., Feng, F., He, M.F.
ID
ZDB-PUB-180913-1
Date
2018
Source
Chinese Journal of Natural Medicines   16: 599-609 (Journal)
Registered Authors
Keywords
1-Methoxycarbony-β-carboline, Angiogenesis inhibitor, Anti-angiogenic index, HUVEC, Zebrafish
MeSH Terms
  • Angiogenesis Inhibitors/chemistry
  • Angiogenesis Inhibitors/pharmacology*
  • Animals
  • Carbolines/chemistry
  • Carbolines/pharmacology*
  • Cell Movement/drug effects
  • Cell Proliferation/drug effects
  • Epidermal Growth Factor/genetics
  • Epidermal Growth Factor/metabolism
  • Fibroblast Growth Factors/genetics
  • Fibroblast Growth Factors/metabolism
  • Human Umbilical Vein Endothelial Cells/cytology
  • Human Umbilical Vein Endothelial Cells/drug effects*
  • Human Umbilical Vein Endothelial Cells/metabolism
  • Humans
  • Insulin-Like Growth Factor I/genetics
  • Insulin-Like Growth Factor I/metabolism
  • Neovascularization, Physiologic/drug effects*
  • Picrasma/chemistry*
  • Plant Extracts/chemistry
  • Plant Extracts/pharmacology*
  • Receptor, TIE-2/genetics
  • Receptor, TIE-2/metabolism
  • Zebrafish/embryology*
PubMed
30197125 Full text @ Chin. J. Nat. Med.
Abstract
Angiogenesis is a crucial process in the development of inflammatory diseases, including cancer, psoriasis and rheumatoid arthritis. Recently, several alkaloids from Picrasma quassioides had been screened for angiogenic activity in the zebrafish model, and the results indicated that 1-methoxycarbony-β-carboline (MCC) could effectively inhibit blood vessel formation. In this study, we further confirmed that MCC can inhibit, in a concentration-dependent manner, the viability, migration, invasion, and tube formation of human umbilical vein endothelial cells (HUVECs) in vitro, as well as the regenerative vascular outgrowth of zebrafish caudal fin in vivo. In the zebrafish xenograft assay, MCC inhibited the growth of tumor masses and the metastatic transplanted DU145 tumor cells. The proteome profile array of the MCC-treated HUVECs showed that MCC could down-regulate several angiogenesis-related self-secreted proteins, including ANG, EGF, bFGF, GRO, IGF-1, PLG and MMP-1. In addition, the expression of two key membrane receptor proteins in angiogenesis, TIE-2 and uPAR, were also down-regulated after MCC treatment. Taken together, these results shed light on the potential therapeutic application of MCC as a potent natural angiogenesis inhibitor via multiple molecular targets.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping