Inhibition of endothelial cell functions and of angiogenesis by the metastasis inhibitor NAMI-A.
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.
Vacca
A
A
Department of Biomedical Sciences and Human Oncology, University of Bari, Policlinico, Piazza Giulio Cesare 11, I-70124 Bari, Italy.
Bruno
M
M
Boccarelli
A
A
Coluccia
M
M
Ribatti
D
D
Bergamo
A
A
Garbisa
S
S
Sartor
L
L
Sava
G
G
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects; D004121:Dimethyl Sulfoxide / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D009942:Organometallic Compounds / Q000494:pharmacology*; D017975:Ruthenium Compounds
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D061965:Matrix Metalloproteinase Inhibitors; D009942:Organometallic Compounds; D017975:Ruthenium Compounds; C113661:imidazolium-bis(imidazole)dimethylsulfoxideimidazotetrachlororuthenate(III); D004121:Dimethyl Sulfoxide