title: Sanguinarine is a novel VEGF inhibitor involved in the suppression of angiogenesis and cell migration.
abstract: Vascular endothelial growth factor (VEGF) is a main angiogenic factor which is known to be upregulated in lung cancer. In the present study, it was demonstrated that sanguinarine, an alkaloid obtained from the bloodroot plant, markedly repressed the VEGF-induced tube formation of human microvascular endothelial cells (HMVECs) and the migration of human A549 lung cancer cells. Furthermore, sanguinarine decreased VEGF secretion and expression in HMVECs and A549 lung cancer cells in a dose- and time-dependent manner. Additionally, sanguinarine inhibited the activation of serum starvation- and hypoxia-induced VEGF promoter activity. Sanguinarine also inhibited the VEGF-mediated Akt and p38 activation, as well as VE-cadherin protein phosphorylation. To the best of our knowledge, this is the first study demonstrating that VEGF inhibition appears to be an important mechanism involved in the antiangiogenic and anti-invasive activities of sanguinarine in lung cancer treatment.
authors.affiliation: School of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou, Jiangsu 215123, P.R. China ;
authors.forename: Jia-Ying
authors.initials: JY
authors.lastname: Xu
authors.affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057, USA.
authors.forename: Qing-Hui
authors.initials: QH
authors.lastname: Meng
authors.affiliation: School of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou, Jiangsu 215123, P.R. China ;
authors.forename: Yu
authors.initials: Y
authors.lastname: Chong
authors.affiliation: School of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou, Jiangsu 215123, P.R. China ;
authors.forename: Yang
authors.initials: Y
authors.lastname: Jiao
authors.affiliation: School of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou, Jiangsu 215123, P.R. China ;
authors.forename: Lin
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057, USA.
authors.forename: Eliot M
authors.initials: EM
authors.lastname: Rosen
authors.affiliation: School of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou, Jiangsu 215123, P.R. China ;
authors.forename: Saijun
authors.initials: S
authors.lastname: Fan
keywords: human microvascular endothelial cells; lung cancer cells; sanguinarine; vascular endothelial growth factor