| 3, 4-dimethoxystilbene, a resveratrol derivative with anti-angiogenic effect, induces both macroautophagy and apoptosis in endothelial cells. | |
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MedLine Citation:
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PMID: 23059970 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. J. Cell. Biochem. © 2012 Wiley Periodicals, Inc. |
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Authors:
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Lu Zhang; Hongjuan Jing; Liuqing Cui; Huanqing Li; Bo Zhou; Guangzhou Zhou; Fang Dai |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-10-11 |
Journal Detail:
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Title: Journal of cellular biochemistry Volume: - ISSN: 1097-4644 ISO Abbreviation: J. Cell. Biochem. Publication Date: 2012 Oct |
Date Detail:
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Created Date: 2012-10-12 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8205768 Medline TA: J Cell Biochem Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2012 Wiley Periodicals, Inc. |
Affiliation:
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College of Bioengineering, Henan University of Technology, Lianhua Street, Zhengzhou, 450001, China. chaperones@163.com. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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