Antiangiogenic potential of 10-hydroxycamptothecin

To investigate the antiangiogenic potential of 10-hydroxycamptothecin (HCPT ), the proliferation of human microvascular endothelial cells (HMEC) and se ven human tumor cell lines were detected by SRB assay, and the endothelial cell migration and tube formation were assessed using two in vitro model sy stems. Also, inhibition of angiogenesis was determined with a modification of the chick embryo chorioallantoic membrane (CAM) assay in vivo. Morpholog ical assessment of apoptosis was performed by fluorescence microscope. HCPT 0.313-5 mu mol.L-1 treatment resulted in a dose-dependent inhibition of pr oliferation, migration and tube formation in HMEC cells, and HCPT 6.25-25 n mol.egg(-1) inhibited angiogenesis in CAM assay. HCPT 1.25-5 mu mo1.L-1 eli cited typical morphological changes of apoptosis including condensed chroma tin, nuclear fragmentation, and reduction in volume in HMEC cells. HCPT sig nificantly inhibited angiogenesis both in vitro and in vivo at relatively l ow concentrations, and this effect was related with induction of apoptosis in HMEC cells. These results taken collectively suggest that HCPT may be a potent antiangiogenetic and cytotoxic drug and further investigation is war ranted. (C) 2001 Elsevier Science Inc. All rights reserved.