A novel RGDS-analog inhibits angiogenesis in vitro and in vivo

M. S. Aguzzi, F. Facchiano, D. Ribatti, R. Gaeta, R. Casadio, I. Rossi, M. C. Capogrossi, A. Facchiano

Research output: Contribution to journalArticlepeer-review

Abstract

In this study the anti-angiogenic action of a novel non-peptide RGDS-analog named RAM was tested in vitro and in vivo. RAM inhibited FGF-2-induced chemotaxis by 80% in an adhesion-independent way. Further, it induced HUVEC-apoptosis in collagen-seeded HUVEC, indicating that such pro-apoptotic effect was adhesion-independent. In vivo studies revealed that RAM inhibited FGF-2 induced angiogenesis by 60% in the mouse Matrigel-assay and in the chicken-egg chorion-allantoic membrane assay. Finally, RAM was markedly more stable in serum as compared to the template RGDS and after 24 h incubation in 100% serum was significantly more active than RGDS. Taken together these results show that RAM exerts anti-chemotactic and pro-apoptotic effects, by an unexpected adhesion-independent mechanism, as we have recently shown for the template RGDS molecule [Blood 103 (2004) 4180], and has in vivo relevant anti-angiogenic properties, with marked stability in serum; therefore, RAM represents a novel promising anti-angiogenic molecule.

Original languageEnglish
Pages (from-to)809-814
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume321
Issue number4
DOIs
Publication statusPublished - Sep 3 2004

Keywords

  • Adhesion
  • Angiogenesis
  • Apoptosis
  • Cell-matrix interactions
  • Endothelial cells
  • Integrins

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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