Psammaplin A, a Marine Natural Product, Inhibits Aminopeptidase N and Suppresses Angiogenesis in Vitro

Cancer Lett. 2004 Jan 20;203(2):163-9. doi: 10.1016/j.canlet.2003.08.036.

Abstract

Psammaplin A (PsA) is a phenolic natural product isolated from a marine sponge, which showed a potent cytotoxicity against several cancer cell lines. In present study, PsA was found to inhibit mammalian aminopeptidase N (APN) that plays a key role in tumor cell invasion and angiogenesis. PsA inhibited the APN activity with an IC50 of 18 microM in a non-competitive manner. Moreover, PsA potently inhibited the proliferation of several cancer and endothelial cells. Interestingly, the anti-proliferative effect of PsA was dependent on the cellular amount of APN expression. Finally, PsA suppressed the invasion and tube formation of endothelial cells stimulated by basic fibroblast growth factor. These data demonstrate that PsA is a new inhibitor of APN and can be developed as a novel anti-angiogenic agent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / pharmacology
  • Animals
  • CD13 Antigens / antagonists & inhibitors*
  • Capillaries / pathology
  • Cattle
  • Cell Division
  • Cell Line, Tumor
  • Cells, Cultured
  • Disulfides / pharmacology*
  • Dose-Response Relationship, Drug
  • Endothelial Cells / metabolism
  • Fibroblast Growth Factor 2 / metabolism
  • In Vitro Techniques
  • Inhibitory Concentration 50
  • Models, Chemical
  • Neoplasm Invasiveness
  • Neovascularization, Pathologic*
  • Porifera
  • Tyrosine / analogs & derivatives*
  • Tyrosine / pharmacology*

Substances

  • Angiogenesis Inhibitors
  • Disulfides
  • Fibroblast Growth Factor 2
  • psammaplin A
  • Tyrosine
  • CD13 Antigens