The designer anti-angiogenic peptide anginex targets tumor endothelial cells and inhibits tumor growth in animal models.
The de novo designed angiogenesis inhibitor anginex was tested in vitro and in vivo for its mechanism of action and antitumor activity. The data presented here demonstrate that anginex is a powerful antiangiogenic agent with significant antitumor activity. The mechanism of action of anginex was found to be the induction of anoikis leading to apoptosis in angiogenically activated endothelial cells, resulting in an up to 90% inhibition of migration in the wound assay. Anginex inhibited angiogenesis as demonstrated in the in vitro mouse aortic ring assay. In addition, tumor-induced angiogenesis in the chick chorioallantoic membrane was markedly inhibited. Anginex showed profound antitumor activity in the syngeneic mouse B16F10 melanoma model and in a xenograft human tumor model. Microvessel density determination as well as magnetic resonance imaging showed that the antitumor activity in these tumor models resulted from the antiangiogenic activity of anginex. A complete absence of toxicity was observed in these models. The data presented here demonstrate that anginex is a promising agent for further clinical development.
van der Schaft
Daisy W J
DW
Angiogenesis Laboratory, Department of Internal Medicine, Research Institute for Growth and Development (GROW), Maastricht University and University Hospital Maastricht, Maastricht, The Netherlands.
Dings
Ruud P M
RP
de Lussanet
Quido G
QG
van Eijk
Loes I
LI
Nap
Annemiek W
AW
Beets-Tan
Regina G H
RG
Bouma-Ter Steege
Jessica C A
JC
Wagstaff
John
J
Mayo
Kevin H
KH
Griffioen
Arjan W
AW
D020533:Angiogenesis Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D016503:Drug Delivery Systems; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology; D051379:Mice; D008954:Models, Biological; D009374:Neoplasms, Experimental / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D010455:Peptides / Q000494:pharmacology / Q000627:therapeutic use; D011506:Proteins / Q000494:pharmacology* / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D010455:Peptides; D011506:Proteins; C111993:betapep-25 protein, synthetic