Inhibition of endothelial cell functions and of angiogenesis by the metastasis inhibitor NAMI-A

Abstract

NAMI-A is a ruthenium-based compound with selective anti-metastasis activity in experimental models of solid tumours. We studied whether this activity was dependent on anti-angiogenic ability of NAMI-A. We thus investigated its in vitro effects on endothelial cell functions necessary for angiogenesis to develop, as well as its in vivo effects in the chick embryo chorioallantoic membrane model. Endothelial cell proliferation, chemotaxis, and secretion of the matrix-degrading enzyme metalloproteinase-2 were inhibited by NAMI-A in a dose-dependent manner, and without morphologic signs of cell apoptosis or necrosis. Lastly, NAMI-A displayed a dose-dependent in vivo anti-angiogenic activity in the chorioallantoic membrane model. These data suggest that the anti-angiogenic activity of NAMI-A can contribute to its anti-metastatic efficacy in mice bearing malignant solid tumours.

Antiangiogenic properties of selected ruthenium(III) complexes that are nitric oxide scavengers

“…The results of this study confirm recent findings on NAMI-A demonstrating its inhibitory activity on proliferation, cell migration and production of degradative enzymes (Vacca et al, 2002;Sanna et al, 2002). Also the antiangiogenic properties previously observed in the chorioallantoic membrane (Vacca et al, 2002) are confirmed in our in vivo assay in the rabbit cornea.…”

“…Also the antiangiogenic properties previously observed in the chorioallantoic membrane (Vacca et al, 2002) are confirmed in our in vivo assay in the rabbit cornea.…”

“…Among these agents, NAMI-A, a compound found to be active against lung metastases (Sava and Bergamo, 1999), tumour cell invasion (Zorzet et al, 2000), and recently to possess antiangiogenesis properties Sanna et al, 2002;Vacca et al, 2002) is presently undergoing clinical trials as an antimetastatic agent.…”

“…These compounds have been shown to exhibit pharmacological activity in vitro and in a number of in vivo models for a variety of diseases including cancer (Clarke, 2002 and references therein). Furthermore, an angiogenesis inhibitory activity has been reported for NAMI-A (imidazolium trans-imidazole dimethylsulphoxide tetrachloro ruthenate, ImH[trans-RuCl4(DMSO)Im) Vacca et al, 2002), a novel ruthenium(III)-based compound developed for selectively treating solid tumour metastases (Sava and Bergamo, 1999).…”

Nitric oxide synthase and NAD(P)H oxidase modulate coronary endothelial cell growth

“…However, in several pathological conditions e.g. tumor metastasis and atherosclerosis endothelial cells proliferate and migrate at greater levels and in an uncontrolled manner [4,5].…”