Antiangiogenesis response of endothelial cells to the antitumour drug 10-methoxy-9-nitrocamptothecin

Pharmacol Res. 2006 Nov;54(5):334-40. doi: 10.1016/j.phrs.2006.06.001. Epub 2006 Jun 30.

Abstract

10-Methoxy-9-nitrocamptothecin (MONCPT), a topoisomerase I inhibitor, exhibited high anticancer activity in solid tumour xenograft animal models in our previous study. We hypothesized that this phenomenon was associated with antiangiogenesis response. In the present study, we found that MONCPT exhibited high antiproliferation action in human EA.hy926 endothelial cells and the IC(50) value was 0.13+/-0.04microM (MTT assay). With AO/EB stain, MONCPT (50-5000nM)-mediated apoptosis was observed in EA.hy926 cells, and the similar results were shown in flow cytometry assay, the percentage of apoptotic cells induced by MONCPT (50-5000nM) was 9.2-58.5%. In Chick embryo chorioallantoic membrane (CAM) assay, MONCPT (1-5microg) resulted in a dose-dependent angiogenic inhibition. In addition, MONCPT significantly inhibited chemotactic-migration invasion on gelatin and tube formation on Matrigel of HUVECs. These results suggest that MONCPT has potential property for inhibiting angiogenesis which is involved in its antitumour activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / pharmacology*
  • Animals
  • Apoptosis
  • Camptothecin / analogs & derivatives*
  • Camptothecin / pharmacology
  • Cell Line
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Chick Embryo
  • Endothelial Cells / drug effects*
  • Endothelial Cells / pathology
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Topoisomerase I Inhibitors

Substances

  • 10-methoxy-9-nitrocamptothecin
  • Angiogenesis Inhibitors
  • Enzyme Inhibitors
  • Topoisomerase I Inhibitors
  • Camptothecin