title: Pharmacological Activities of Ruthenium Complexes Related to Their NO Scavenging Properties.
abstract: Angiogenesis is considered responsible for the growth of primary tumours and of their metastases. With the present study, the effects of three ruthenium compounds, potassiumchlorido (ethylendiamminotetraacetate)rutenate(III) (RuEDTA), sodium (bis-indazole)tetrachloro-ruthenate(III), Na[trans-RuCl₄Ind₂] (KP1339) and trans-imidazoledimethylsulphoxidetetrachloro-ruthenate (NAMI-A), are studied in vitro in models mimicking the angiogenic process. The ruthenium compounds reduced the production and the release of nitrosyls from either healthy macrophages and immortalized EA.hy926 endothelial cells. The effects of NAMI-A are qualitatively similar and sometimes quantitatively superior to those of RuEDTA and KP1339. NAMI-A reduces the production and release of nitric oxide (NO) by the EA.hy926 endothelial cells and correspondingly inhibits their invasive ability; it also strongly inhibits the angiogenesis in matrigel sponges implanted subcutaneously in healthy mice. Taken together, these data support the anti-angiogenic activity of the tested ruthenium compounds and they contribute to explain the selective activity of NAMI-A against solid tumour metastases, the tumour compartment on which angiogenesis is strongly involved. This anti-angiogenic effect may also contribute to the inhibition of the release of metastatic cells from the primary tumour. Investigations on the anti-angiogenic effects of NAMI-A at this level will increase knowledge of its pharmacological properties and it will give a further impulse to the development of this class of innovative metal-based drugs.
authors.affiliation: Callerio Foundation Onlus, via A. Fleming 22-31, 34127 Trieste, Italy. anna_fc@yahoo.it.|Department of Life Sciences, University of Trieste, 34127 Trieste, Italy. anna_fc@yahoo.it.
authors.forename: Anna
authors.initials: A
authors.lastname: Castellarin
authors.affiliation: Department of Life Sciences, University of Trieste, 34127 Trieste, Italy. zorzet@units.it.
authors.forename: Sonia
authors.initials: S
authors.lastname: Zorzet
authors.affiliation: Callerio Foundation Onlus, via A. Fleming 22-31, 34127 Trieste, Italy. a.bergamo@callerio.org.
authors.forename: Alberta
authors.initials: A
authors.lastname: Bergamo
authors.affiliation: Callerio Foundation Onlus, via A. Fleming 22-31, 34127 Trieste, Italy. gsava@units.it.|Department of Life Sciences, University of Trieste, 34127 Trieste, Italy. gsava@units.it.
authors.forename: Gianni
authors.initials: G
authors.lastname: Sava
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003094:Collagen / Q000494:pharmacology; D056831:Coordination Complexes / Q000494:pharmacology*; D004338:Drug Combinations; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D007797:Laminin / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000187:drug effects; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism*; D011509:Proteoglycans / Q000494:pharmacology; D012428:Ruthenium / Q000494:pharmacology*
chemical_list: D020533:Angiogenesis Inhibitors; D056831:Coordination Complexes; D004338:Drug Combinations; D016166:Free Radical Scavengers; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D009569:Nitric Oxide; D012428:Ruthenium; D003094:Collagen
keywords: angiogenesis; anticancer; cell cultures; nitric oxide; ruthenium