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

Document Type

Journal Article

Publication Date

2010

DOI

10.1002/jcb.22405

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.

Source Publication

Journal of Cellular Biochemistry

Volume Number

109

Issue Number

2

First Page

339

Last Page

346

This document is currently not available here.

Link to Publisher’s Version

Share

COinS