Anti-tumor activity of the novel angiogenesis inhibitor anginex

Ruud P.M. Dings, Daisy W.J. Van Der Schaft, Balazs Hargittai, Judy Haseman, Arjan W. Griffioen, Kevin H. Mayo

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

Abstract

Anginex is a novel cytokine-like peptide with potent anti-angiogenic activity, which operates specifically against angiogenically-activated endothelial cells via prevention of cell adhesion/migration on the extracellular matrix and subsequent induction of apoptosis. Here, we demonstrate that anginex inhibits tumor growth in vivo in mouse xenograft models. In the MA148 ovarian carcinoma model, tumor growth was inhibited dose-dependently by up to 80% when systemically administered via osmotic mini-pumps starting at the time of tumor cell inoculation. The optimal dose was found to be 10 mg/kg per day. When tested against established tumors, mini-pump-administered anginex demonstrated essentially the same effectivity at this optimal dose, whereas once or twice-daily injections were only half as effective. When anginex was conjugated to human serum albumin, effectivity was significantly improved, most likely due to increased bioavailability of the conjugate. Immunohistochemical analysis of microvessel density indicated that the anti-tumor activity of anginex is mediated by angiogenesis inhibition. This was confirmed in an in vitro angiogenesis assay based on tube formation in a collagen gel. Animals demonstrated no signs of toxicity as judged by unaltered behavior, normal weight gain, blood markers and macro- and microscopic morphology of internal organs upon autopsy. Overall, these in vivo studies indicate that anginex is an effective anti-tumor agent.

Original languageEnglish (US)
Pages (from-to)55-66
Number of pages12
JournalCancer Letters
Volume194
Issue number1
DOIs
StatePublished - May 8 2003

Keywords

  • Anginex
  • Angiogenesis
  • Bioavailability
  • Conjugation
  • Microvessel density
  • Systemic treatment

Fingerprint Dive into the research topics of 'Anti-tumor activity of the novel angiogenesis inhibitor anginex'. Together they form a unique fingerprint.

Cite this