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
-
- Animals
- Animals, Genetically Modified
- Cell Cycle*
- Cell Line, Tumor
- Cell Proliferation
- Down-Regulation/drug effects
- Embryo, Nonmammalian/cytology
- Embryo, Nonmammalian/physiology
- Endothelial Cells/cytology
- Endothelial Cells/drug effects*
- Humans
- Neovascularization, Physiologic/drug effects*
- Stilbenes/chemistry
- Stilbenes/pharmacology*
- Transcription, Genetic/drug effects
- Umbilical Veins/cytology
- Vascular Endothelial Growth Factor Receptor-2/genetics*
- Vascular Endothelial Growth Factor Receptor-2/metabolism
- Zebrafish/embryology
- Zebrafish/genetics*
- Zebrafish/metabolism
- PubMed
- 20014068 Full text @ J. Cell. Biochem.
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.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping