PUBLICATION

The noni anthraquinone damnacanthal is a multi-kinase inhibitor with potent anti-angiogenic effects

Authors
García-Vilas, J.A., Pino-Ángeles, A., Martínez-Poveda, B., Quesada, A.R., Medina, M.Á.
ID
ZDB-PUB-170809-9
Date
2017
Source
Cancer letters   385: 1-11 (Journal)
Registered Authors
Keywords
Angiogenesis, Damnacanthal, Morinda citrifolia, Multi-kinase inhibitor, Noni
MeSH Terms
  • Angiogenesis Inhibitors/chemistry
  • Angiogenesis Inhibitors/pharmacology*
  • Animals
  • Anthraquinones/chemistry
  • Anthraquinones/pharmacology*
  • Cattle
  • Cell Adhesion/drug effects
  • Cell Line
  • Cell Movement/drug effects
  • Cell Proliferation/drug effects
  • Cell Survival/drug effects
  • Chick Embryo
  • Chorioallantoic Membrane/blood supply*
  • Dose-Response Relationship, Drug
  • Extracellular Matrix/drug effects
  • Extracellular Matrix/metabolism
  • Focal Adhesion Kinase 1/antagonists & inhibitors*
  • Focal Adhesion Kinase 1/chemistry
  • Focal Adhesion Kinase 1/metabolism
  • Human Umbilical Vein Endothelial Cells/drug effects*
  • Human Umbilical Vein Endothelial Cells/enzymology
  • Humans
  • Molecular Docking Simulation
  • Molecular Dynamics Simulation
  • Neovascularization, Physiologic/drug effects
  • Protein Conformation
  • Protein Kinase Inhibitors/chemistry
  • Protein Kinase Inhibitors/pharmacology*
  • Proto-Oncogene Proteins c-met/antagonists & inhibitors*
  • Proto-Oncogene Proteins c-met/chemistry
  • Proto-Oncogene Proteins c-met/metabolism
  • Signal Transduction/drug effects
  • Structure-Activity Relationship
  • Zebrafish/embryology
PubMed
27816491 Full text @ Cancer Lett.
Abstract
The natural bioactive compound damnacanthal inhibits several tyrosine kinases. Herein, we show that -in fact- damancanthal is a multi kinase inhibitor. A docking and molecular dynamics simulation approach allows getting further insight on the inhibitory effect of damnacanthal on three different kinases: vascular endothelial growth factor receptor-2, c-Met and focal adhesion kinase. Several of the kinases targeted and inhibited by damnacanthal are involved in angiogenesis. Ex vivo and in vivo experiments clearly demonstrate that, indeed, damnacanthal is a very potent inhibitor of angiogenesis. A number of in vitro assays contribute to determine the specific effects of damnacanthal on each of the steps of the angiogenic process, including inhibition of tubulogenesis, endothelial cell proliferation, survival, migration and production of extracellular matrix remodeling enzyme. Taken altogether, these results suggest that damancanthal could have potential interest for the treatment of cancer and other angiogenesis-dependent diseases.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping