Monocarbonyl curcumin analog A2 potently inhibits angiogenesis by inducing ROS-dependent endothelial cell death

Liu Bin ¹ Cui Liusu ² Zhou Bo ³ Zhang Lingling ¹ Liu Zhihui ¹ Zhang Lu ¹ ^*

文摘	Excessive and abnormal vessel growth plays a critical role in the pathogenesis of many diseases, such as cancer.Angiogenesis is one of the hallmarks of cancer growth, invasion, and metastasis.Discovery of novel antiangiogenic agents would provide new insights into the mechanisms of angiogenesis, as well as potential drugs for cancer treatment.In the present study, we investigated the antiangiogenic activity of a series of monocarbonyl analogs of curcumin synthesized previously in our lab.We found that curcumin analog A2 displayed the full potential to be developed as a novel antiangiogenic agent.Curcumin analog A2 at and above 20 μM dramatically inhibited the migration and tube formation of human umbilical vein endothelial cells(HUVECs)in vitro, new microvessels sprouting from the rat aortic rings ex vivo and newly formed microvessels in chicken chorioallantoic membranes(CAMs)and Matrigel plus in vivo.We further demonstrated that curcumin analog A2 exerted its antiangiogenic activity mainly through inducing endothelial cell death via elevating NADH/NADPH oxidase-derived ROS.Curcumin analog A2 at the antiangiogenic concentrations also triggered autophagy in HUVECs, but this process is neither a pre-requisite for toxicity, leading to the cell death nor a protective response against the toxicity of curcumin analog A2.In conclusion, we demonstrate for the first time the potent antiangiogenic activity of the monocarbonyl curcumin analog A2, which could serve as a promising potential therapeutic agent for the prevention and treatment angiogenesis-related diseases, such as cancer.
来源	Acta Pharmacologica Sinica ,2019,40(11):1412-1423 【核心库】
DOI	10.1038/s41401-019-0224-x
关键词	monocarbonyl curcumin analog ; angiogenesis ; apoptosis ; autophagy ; necroptosis ; reactive oxygen species ; vascular endothelial cell ; bafilomycin A1 ; wortmannin
地址	1. College of Bioengineering, Henan University of Technology, Zhengzhou, 450001 2. Morphological laboratory, Xinxiang Medical University, Xinxiang, 453003 3. Lanzhou University, State Key Laboratory of Applied Organic Chemistry, Lanzhou, 730000
语种	英文
文献类型	研究性论文
ISSN	1671-4083
学科	医药、卫生
基金	国家自然科学基金 ; the Foundation for Key Teacher by Henan University of Technology ; the Research Program for Science and Technology of Henan Province
文献收藏号	CSCD:6609381