In vitro inhibition of endothelial cell growth by the antiangiogenic drug AGM-1470 (TNP-470) and the anti-endoglin antibody TEC-11

Jeanette A M Maier, Domenico Delia, Philip E. Thorpe, Giampietro Gasparini

Research output: Contribution to journalArticle

51 Scopus citations

Abstract

Angiogenesis plays a key role in tumor growth, progression and metastasis. The modulation of angiogenesis represents a potentially useful target for novel forms of anticancer therapy. Two such modulators are AGM-1470 (TNP-470, angioinhibin), which is a synthetic analog of the antibiotic fumagallin, and the monoclonal antibody TEC-11 to endoglin. We investigated the mechanisms of action of these modulators on human microvascular and macrovascular endothelial cells and on the transformed endothelial cell line ECV-304 in vitro. The administration of AGM-1470 or TEC-11 resulted in a significant inhibition of cell proliferation in all cell types used; this effect was reversible upon removal of these compounds from the culture medium. Furthermore, biochemical and morphological analyses showed that neither AGM-1470 or TEC-11 induce apoptosis. Both AGM-1470 and TEC-11 inhibited the production of urokinase-type plasminogen activator (u-PA), an enzyme involved in the early steps of neovascularization. Finally, the incubation of endothelial cells with both AGM-1470 and TEC-11 did not produce an additive effect on growth cell inhibition, apoptosis or u-PA production. Since both AGM-1470 and TEC-11 inhibit crucial events such as endothelial cell growth and protease production, our results provide a basis for their therapeutic use as angiostatic molecules in cancer.

Original languageEnglish (US)
Pages (from-to)238-244
Number of pages7
JournalAnti-Cancer Drugs
Volume8
Issue number3
DOIs
StatePublished - Apr 23 1997

Keywords

  • angiogenesis
  • angiogenesis inhibitors
  • human endothelial cells

ASJC Scopus subject areas

  • Oncology
  • Pharmacology
  • Pharmacology (medical)
  • Cancer Research

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