title: Safrole oxide inhibits angiogenesis by inducing apoptosis.
abstract: Our previous studies indicate that 3, 4-(methylenedioxy)-1-(2', 3'-epoxypropyl)-benzene (safrole oxide), a newly synthesized compound, induces apoptosis in vascular endothelial cells (VECs) and A549 lung cancer cells. To our knowledge, the inhibition of angiogenesis by safrole oxide has not been reported yet. We report here that cultured rat aorta treated with safrole oxide exhibited a significant microvessel reduction as determined by counting the number of microvessels in a phase contrast microscope. There were more microvessels formed in the presence of A549 lung cancer cells in rat aorta model, while a dramatic inhibition of angiogenesis was obtained by adding 220-450 micromol l(-1) of safrole oxide to the growth medium (P<.01). The culture of rat aorta treated with safrole oxide produced only some abortive endothelial cells but not microvessels. Furthermore, safrole oxide induced antiangiogenic effect in the chorioallantoic membranes (CAM) as a dose dependent manner. Eggs treated with 2-11 micromol 100 microl(-1) per egg of the safrole oxide for 48 h exhibited a significant reduction in blood vessel area of the CAM, a process likely mediated by apoptosis as demonstrated by DNA fragmentation. Our results suggest that safrole oxide has antiangiogenic activity and this effect might occur by induction of cellular apoptosis.
authors.affiliation: Institute of Developmental Biology, School of Life Science, Shandong University, Jinan 250100, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.forename: Junying
authors.initials: J
authors.lastname: Miao
authors.forename: Baoxiang
authors.initials: B
authors.lastname: Zhao
authors.forename: Shangli
authors.initials: S
authors.lastname: Zhang
authors.forename: Deling
authors.initials: D
authors.lastname: Yin
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000187:drug effects; D003094:Collagen / Q000737:chemistry / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis / Q000302:isolation & purification; D053938:DNA Fragmentation / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012451:Safrole / Q000031:analogs & derivatives* / Q000494:pharmacology; D012685:Sepharose / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; C009196:safrole oxide; D003094:Collagen; D004247:DNA; D012685:Sepharose; D012451:Safrole