PUBLICATION

A Novel Poly-Naphthol Compound ST104P Suppresses Angiogenesis by Attenuating Matrix Metalloproteinase-2 Expression in Endothelial Cells

Authors
Ma, Y.L., Lin, S.W., Fang, H.C., Chou, K.J., Bee, Y.S., Chu, T.H., Chang, M.C., Weng, W.T., Wu, C.Y., Cho, C.L., Tai, M.H.
ID
ZDB-PUB-140923-2
Date
2014
Source
International Journal of Molecular Sciences   15: 16611-16627 (Journal)
Registered Authors
Keywords
none
MeSH Terms
  • Angiogenesis Inhibitors/chemistry
  • Angiogenesis Inhibitors/pharmacology*
  • Angiogenesis Inhibitors/therapeutic use
  • Angiogenesis Inhibitors/toxicity
  • Animals
  • Animals, Genetically Modified
  • Aorta
  • Carcinoma, Lewis Lung/blood supply
  • Carcinoma, Lewis Lung/drug therapy
  • Cell Movement/drug effects
  • Down-Regulation/drug effects
  • Drug Evaluation, Preclinical
  • Embryo, Nonmammalian/blood supply
  • Embryo, Nonmammalian/drug effects
  • Endothelium, Vascular/drug effects*
  • Endothelium, Vascular/enzymology
  • Enzyme Induction/drug effects
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Macrocyclic Compounds/chemistry
  • Macrocyclic Compounds/pharmacology*
  • Macrocyclic Compounds/therapeutic use
  • Macrocyclic Compounds/toxicity
  • Matrix Metalloproteinase 2/biosynthesis*
  • Mice
  • Mice, Inbred C57BL
  • Morphogenesis/drug effects
  • Naphthalenesulfonates/chemistry
  • Naphthalenesulfonates/pharmacology*
  • Naphthalenesulfonates/therapeutic use
  • Naphthalenesulfonates/toxicity
  • Neovascularization, Pathologic/drug therapy
  • Neovascularization, Physiologic/drug effects*
  • Zebrafish/embryology
PubMed
25244013 Full text @ Int. J. Mol. Sci.
Abstract
Angiogenesis, the process of neovascularization, plays an important role in physiological and pathological conditions. ST104P is a soluble polysulfated-cyclo-tetrachromotropylene compound with anti-viral and anti-thrombotic activities. However, the functions of ST104P in angiogenesis have never been explored. In this study, we investigated the effects of ST104P in angiogenesis in vitro and in vivo. Application of ST104P potently suppressed the microvessels sprouting in aortic rings ex vivo. Furthermore, ST104P treatment significantly disrupted the vessels' development in transgenic zebrafish in vivo. Above all, repeated administration of ST104P resulted in delayed tumor growth and prolonged the life span of mice bearing Lewis lung carcinoma. Mechanistic studies revealed that ST104P potently inhibited the migration, tube formation and wound closure of human umbilical endothelial cells (HUVECs). Moreover, ST104P treatment inhibited the secretion and expression of matrix metalloproteinase-2 (MMP-2) in a dose-dependent manner. Together, these results suggest that ST104P is a potent angiogenesis inhibitor and may hold potential for treatment of diseases due to excessive angiogenesis including cancer.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping