3,4-dimethoxystilbene, a resveratrol derivative with anti-angiogenic effect, induces both macroautophagy and apoptosis in endothelial cells
| Autor: | Fang Dai, Hongjuan Jing, Lu Zhang, HuanQing Li, Bo Zhou, LiuQing Cui, GuangZhou Zhou |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Small interfering RNA
Cell Survival Angiogenesis Neovascularization Physiologic Angiogenesis Inhibitors Apoptosis AMP-Activated Protein Kinases Resveratrol Biology Biochemistry Autophagy-Related Protein 5 Cell Line chemistry.chemical_compound Cell Movement Stilbenes Autophagy Human Umbilical Vein Endothelial Cells Humans RNA Small Interfering Molecular Biology Cell Proliferation bcl-2-Associated X Protein chemistry.chemical_classification Tube formation Reactive oxygen species Caspase 3 Adenine TOR Serine-Threonine Kinases fungi Cytochromes c Cell Biology Caspase 9 Cell biology Endothelial stem cell chemistry Calcium RNA Interference Tumor Suppressor Protein p53 Reactive Oxygen Species Microtubule-Associated Proteins |
| Zdroj: | Journal of Cellular Biochemistry. 114:697-707 |
| ISSN: | 0730-2312 |
| DOI: | 10.1002/jcb.24411 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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