We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
3,4-Dimethoxystilbene, a resveratrol derivative with anti-angiogenic effect, induces both macroautophagy and apoptosis in endothelial cells.
- Authors
Zhang, Lu; Jing, HongJuan; Cui, LiuQing; Li, HuanQing; Zhou, Bo; Zhou, GuangZhou; Dai, Fang
- Abstract
Angiogenesis plays an important role in many pathological processes. Identification of novel anti-angiogenic agents will provide new insights into the mechanisms for angiogenesis as well as potential lead compounds for developing new drugs. In the present study, a series of resveratrol methylated derivatives have been synthesized and screened. We found trans-3,4-dimethoxystilbene (3,4-DMS) with the fullest potential to develop as an anti-angiogenic agent. In vitro and in vivo analyses suggested that 3,4-DMS could effectively inhibit endothelial cell proliferation, migration, tube formation, and endogenous neovascularization. Our results showed that 3,4-DMS exerted its anti-angiogenic effect likely through induction of endothelial cell apoptosis via a pathway involving p53, Bax, cytochrome c, and caspase proteases. Moreover, 3,4-DMS also induced macroautophagy in endothelial cells through activation of AMPK and the downstream inhibition of mTOR signaling pathway. Further studies indicated that intracellular calcium ([Ca(2+)](i)) might bridge the 3,4-DMS-induced apoptosis and macroautophagy through modulating reactive oxygen species (ROS) levels in endothelial cells. Combination of 3,4-DMS with inhibitor of autophagy, such as 3-methyladenine (3-MA) and autophagy-related gene (ATG) 5 small interfering RNA (siRNA), potentiated the pro-apoptotic and anti-angiogenic effects of 3,4-DMS. Our study provides a novel angiogenic inhibitor and a useful tool in exploring the molecular mechanisms for the crosstalk between apoptosis and macroautophagy in endothelial cells. 3,4-DMS could be served as a potential lead compound for developing a class of new drugs targeting angiogenesis-related diseases.
- Publication
Journal of cellular biochemistry, 2013, Vol 114, Issue 3, p697
- ISSN
1097-4644
- Publication type
Journal Article
- DOI
10.1002/jcb.24411