PUBLICATION

Resveratrol derivative, trans-3,5,4'-trimethoxystilbene, exerts antiangiogenic and vascular-disrupting effects in zebrafish through the downregulation of VEGFR2 and cell-cycle modulation

Authors
Alex, D., Leong, E.C., Zhang, Z.J., Yan, G.T., Cheng, S.H., Leong, C.W., Li, Z.H., Lam, K.H., Chan, S.W., and Lee, S.M.
ID
ZDB-PUB-091221-21
Date
2010
Source
Journal of cellular biochemistry   109(2): 339-346 (Journal)
Registered Authors
Cheng, Shuk Han
Keywords
3,5,4-trimethoxystilbene, angiogenesis, HUVEC, zebrafish, VEGFR2, cell cycle
MeSH Terms
  • Down-Regulation/drug effects
  • Animals, Genetically Modified
  • Embryo, Nonmammalian/cytology
  • Embryo, Nonmammalian/physiology
  • Transcription, Genetic/drug effects
  • Animals
  • Zebrafish/embryology
  • Zebrafish/genetics*
  • Zebrafish/metabolism
  • Neovascularization, Physiologic/drug effects*
  • Humans
  • Stilbenes/chemistry
  • Stilbenes/pharmacology*
  • Cell Proliferation
  • Cell Cycle*
  • Vascular Endothelial Growth Factor Receptor-2/genetics*
  • Vascular Endothelial Growth Factor Receptor-2/metabolism
  • Umbilical Veins/cytology
  • Endothelial Cells/cytology
  • Endothelial Cells/drug effects*
  • Cell Line, Tumor
(all 21)
PubMed
20014068 Full text @ J. Cell. Biochem.
Abstract
Angiogenesis plays an important role in the development of neoplastic diseases such as cancer. Resveratrol and its derivatives exert antiangiogenic effects, but the mechanisms of their actions remain unclear. The aim of this study was to evaluate the antiangiogenic activity of resveratrol and its derivative trans-3,5,4'-trimethoxystilbene in vitro using human umbilical vein endothelial cells (HUVECs) and in vivo using transgenic zebrafish, and to clarify their mechanisms of action in zebrafish by gene expression analysis of the vascular endothelial growth factor (VEGF) receptor (VEGFR2/KDR) and cell-cycle analysis. trans-3,5,4'-Trimethoxystilbene showed significantly more potent antiangiogenic activity than that of resveratrol in both assays. In zebrafish, trans-3,5,4'-trimethoxystilbene caused intersegmental vessel regression and downregulated VEGFR2 mRNA expression. Trans-3,5,4'-trimethoxystilbene also induced G2/M cell-cycle arrest, most specifically in endothelial cells of zebrafish embryos. We propose that the antiangiogenic and vascular-targeting activities of trans-3,5,4'-trimethoxystilbene result from the downregulation of VEGFR2 expression and cell-cycle arrest at G2/M phase.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
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Citation
Alex, D., Leong, E.C., Zhang, Z.J., Yan, G.T., Cheng, S.H., Leong, C.W., Li, Z.H., Lam, K.H., Chan, S.W., and Lee, S.M. (2010) Resveratrol derivative, trans-3,5,4'-trimethoxystilbene, exerts antiangiogenic and vascular-disrupting effects in zebrafish through the downregulation of VEGFR2 and cell-cycle modulation. Journal of cellular biochemistry. 109(2):339-346.