title: Effects of the ruthenium-based drug NAMI-A on the roles played by TGF-β1 in the metastatic process.
abstract: The ruthenium-based drug NAMI-A, characterised by its selectivity against solid tumour metastases, promotes TGF-β1-dependent fibrosis and the reduction of the release of MMPs in the primary tumour. The aim of the study was to examine the interaction of NAMI-A with TGF-β1 in the process of metastasis formation. NAMI-A (1) affects the secretion of TGF-β1 in metastatic MDA-MB-231 cells rather than in non-tumorigenic HBL-100 cells, (2) prevails over TGF-β1 with regard to the invasive capacity of the treated cells, and (3) contrasts integrin-dependent migration stimulated by TGF-β1. It, thus, appears that the effects of NAMI-A on cell invasion and migration are best summarised as an interference with TGF-β1 and a reduction of its activity in these events. At a molecular level, the similar activity of NAMI-A and TGF-β1 on RhoA GTPase supports its interaction with cell surface integrins while TGF-β1 can activate it by interaction with its TGFβR receptor. The inhibition of TGF-β1-induced migration of MDA-MB-231 cells by NAMI-A cannot simply be attributed to a modulation of the Smad2 and p38MAPK pathways. In conclusion, the effects of NAMI-A on the biological role of TGF-β1 in cancer metastasis are insufficient to attribute the responsibility for the anti-metastatic activity of the ruthenium-based drug to this target alone.
authors.affiliation: Callerio Foundation Onlus, via A. Fleming 22, 34127, Trieste, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Brescacin
authors.affiliation: Callerio Foundation Onlus, via A. Fleming 22, 34127, Trieste, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Masi
authors.affiliation: Callerio Foundation Onlus, via A. Fleming 22, 34127, Trieste, Italy.|Department of Life Sciences, University of Trieste, via A. Fleming 22, 34127, Trieste, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Sava
authors.affiliation: Callerio Foundation Onlus, via A. Fleming 22, 34127, Trieste, Italy. a.bergamo@callerio.org.
authors.forename: A
authors.initials: A
authors.lastname: Bergamo
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004121:Dimethyl Sulfoxide / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D015394:Molecular Structure; D009362:Neoplasm Metastasis / Q000188:drug therapy; D009369:Neoplasms / Q000188:drug therapy / Q000503:physiopathology; D009942:Organometallic Compounds / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D012428:Ruthenium / Q000737:chemistry / Q000494:pharmacology*; D017975:Ruthenium Compounds; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D017975:Ruthenium Compounds; D053773:Transforming Growth Factor beta1; C113661:imidazolium-bis(imidazole)dimethylsulfoxideimidazotetrachlororuthenate(III); D012428:Ruthenium; D004121:Dimethyl Sulfoxide
keywords: Anticancer drug; Biomedicine; Heavy metal; Molecular dynamics