title: Anti-angiogenesis effect of trichosanthin and the underlying mechanism.
abstract: The growth and metastasis of tumors depend on angiogenesis. Tumor angiogenesis is initiated by the secretion of growth factors from tumor cells; downstream signals are then triggered in pre-existing blood vessels to sprout a new vascular network. Trichosanthin (TCS) is a type I ribosome-inactivating protein that has anti-tumor activity, but the underlying mechanism remains unclear. In this study, we found that a non-toxic dose of TCS decreased the wound-healing and the migration of H5V mouse heart capillary endothelial cells (ECs) induced by human choriocarcinoma (JAR) cells, as well as the JAR-induced angiogenesis of rat third-order mesenteric arteries. TCS was effective on both tumor cells and ECs/arteries. First, TCS decreased vascular endothelial growth factor transcription and secretion by JAR cells. Second, TCS consequently inhibited the tumor cell-induced, extracellular signal-regulated kinase-mediated angiogenic signal in ECs and blood vessels. In conclusion, the ability of TCS to inhibit tumor angiogenesis contributes to its anti-tumor activity.
authors.affiliation: National Engineering Laboratory for Cereal Fermentation Technology, Jiangnan University, Wuxi 214122, China.
authors.forename: Dongxu
authors.initials: D
authors.lastname: He
authors.forename: Jian
authors.initials: J
authors.lastname: Jin
authors.forename: Yongtang
authors.initials: Y
authors.lastname: Zheng
authors.forename: Iain C
authors.initials: IC
authors.lastname: Bruce
authors.forename: Siucheung
authors.initials: S
authors.lastname: Tam
authors.forename: Xin
authors.initials: X
authors.lastname: Ma
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects* / Q000502:physiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D051379:Mice; D009369:Neoplasms / Q000098:blood supply*; D051381:Rats; D015978:Trichosanthin / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology
chemical_list: D020533:Angiogenesis Inhibitors; D042461:Vascular Endothelial Growth Factor A; D015978:Trichosanthin; D048049:Extracellular Signal-Regulated MAP Kinases