Study On The Effect And Mechanism Of Curcumin Analog A2 Inhibiting Angiogenesis

Angiogenesis is an important link in cancer growth,invasion and metastasis,including atherosclerosis,hypertension,miocardial infarction.Exploring novel anti-angiogenic inhibitors would provide new insights into the mechanisms for angiogenesis as well as treatment of angiogenesis-related diseases.In the present study,a series of previously synthesized monocarbonyl analogs of curcumin in our lab were screened and characterized for their anti-angiogenic properties.Among these compounds,we found that curcumin analog A2 has the fullest potential to develop as an anti-angiogenic inhibitor.We demonstrated that curcumin analog A2 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 micro-vessels in chicken chorioallantoic membranes(CAMs)and Matrigel plus in vivo at the concentrations equal to or above 20 ?M.We further investigated the mechanism by which curcumin analogue A2 inhibits angiogenesis and found that A2 induced apoptosis,necroptosis and autophagy via NADH/NADPH-induced Reactive Oxygen Species(ROS)elevation in HUVECs.We demonstrated for the first time that monocarbonyl curcumin analogue A2 is a novel angiogenesis inhibitor,which is expected to be a powerful tool for the research on molecular mechanisms involved in angiogenesis,as well as a promising potential therapeutic agent for the prevention and treatment angiogenesis-related diseases,such as cancer.