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

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 IC50 value was 0.13 +/- 0.04 mu M (MTT assay). With AO/EB stain, MONCPT (50-5000 nM)-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 (1-5 mu g) 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. (c) 2006 Elsevier Ltd. All rights reserved.