QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: mol.107.036350v1 72/3/545    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tian, F. Articles by Ding, J. Search for Related Content PubMed PubMed Citation Articles by Tian, F. Articles by Ding, J.

Philinopside E, a New Sulfated Saponin from Sea Cucumber, Blocks the Interaction between Kinase Insert Domain-Containing Receptor (KDR) and _v3 Integrin via Binding to the Extracellular Domain of KDR

Division of Antitumor Pharmacology, State Key Laboratory of Drug Research (F.T., C.Z., X.Z., L.L., M.G., J.D.), National Center for Drug Screening (X.X.), Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, People's Republic of China; Department of Pharmacology and Glycobiology, Marine Drug and Food Institute, Ocean University of China, Qingdao, People's Republic of China (X.X., M.G.); and Research Center for Marine Drugs, School of Pharmacy, Second Military Medical University, Shanghai, People's Republic of China (Y.Y.)

Vascular endothelial growth factor (VEGF) signaling pathway is essential for tumor angiogenesis and has long been recognized as a promising target for cancer therapy. Current view holds that physical interaction between _v3 integrin and kinase insert domain-containing receptor (KDR) is important in regulating angiogenesis and tumor development. We have reported previously that a new marine-derived compound, philinopside E (PE), exhibited the antiangiogenic activity via inhibition on KDR phosphorylation and downstream signaling. Herein, we have further demonstrated that PE specifically interacts with KDR extracellular domain, which is distinct from conventional small-molecule inhibitors targeting cytoplasmic kinase domain, to block its interaction with VEGF and the downstream signaling. We also noted that PE markedly suppresses _v3 integrin-driven downstream signaling as a result of disturbance of the physical interaction between KDR and _v3 integrin in HMECs, followed by disruption of the actin cytoskeleton organization and decreased cell adhesion to vitronectin. All of these findings substantiate PE to be an unrecognized therapeutic class in tumor angiogenesis and, more importantly, help appeal the interest of the therapeutic potential in angiogenesis and cancer development via targeting integrin-KDR interaction in the future.

Address correspondence to: Dr. Jian Ding, Division of Antitumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, P.R. China. E-mail: jding{at}mail.shcnc.ac.cn

This article has been cited by other articles:

				G. Serini, L. Napione, M. Arese, and F. Bussolino Besides adhesion: new perspectives of integrin functions in angiogenesis Cardiovasc Res, May 1, 2008; 78(2): 213 - 222. [Abstract] [Full Text] [PDF]