caa a22 4500 605507139 CHVBK 20210128100630.0 cr unu---uuuuu 210128e20151001xx s 000 0 eng 10.1007/s00775-015-1297-8 doi (NATIONALLICENCE)springer-10.1007/s00775-015-1297-8 Effects of the ruthenium-based drug NAMI-A on the roles played by TGF-β1 in the metastatic process [Elektronische Daten] [L. Brescacin, A. Masi, G. Sava, A. Bergamo] 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. Graphical Abstract: SBIC, 2015 Anticancer drug nationallicence Heavy metal nationallicence Biomedicine nationallicence Molecular dynamics nationallicence BSA : Bovine serum albumin nationallicence CHK1 : Checkpoint kinase 1 nationallicence CMF-DPBS : Calcium and Magnesium Free Dulbecco's Phosphate Buffered Saline nationallicence ECM : Extracellular matrix nationallicence DMEM : Dulbecco's modified Eagle's medium nationallicence DPBS : Dulbecco's Phosphate Buffered Saline nationallicence FBS : Foetal bovine serum nationallicence GRP78 : 78kDa glucose-regulated protein nationallicence LB : Lysis buffer nationallicence MMPs : Matrix metallo proteinases nationallicence NAMI-A : Imidazolium trans-imidazoletetrachlororuthenate nationallicence ROS : Reactive oxygen species nationallicence SRB : Sulforhodamine B nationallicence TCA : Trichloro acetic acid nationallicence TGF-β1 : Transforming growth factor beta 1 nationallicence TIMPs : Tissue inhibitors of MMPs nationallicence TMB : 3,3′,5,5′-Tetramethylbenzidine nationallicence Brescacin L. Callerio Foundation Onlus, via A. Fleming 22, 34127, Trieste, Italy aut Masi A. Callerio Foundation Onlus, via A. Fleming 22, 34127, Trieste, Italy aut Sava G. Callerio Foundation Onlus, via A. Fleming 22, 34127, Trieste, Italy aut Bergamo A. Callerio Foundation Onlus, via A. Fleming 22, 34127, Trieste, Italy aut JBIC Journal of Biological Inorganic Chemistry Springer Berlin Heidelberg 20/7(2015-10-01), 1163-1173 0949-8257 20:7<1163 2015 20 775 https://doi.org/10.1007/s00775-015-1297-8 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00775-015-1297-8 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Brescacin L. Callerio Foundation Onlus, via A. Fleming 22, 34127, Trieste, Italy aut NATIONALLICENCE 700 1- Masi A. Callerio Foundation Onlus, via A. Fleming 22, 34127, Trieste, Italy aut NATIONALLICENCE 700 1- Sava G. Callerio Foundation Onlus, via A. Fleming 22, 34127, Trieste, Italy aut NATIONALLICENCE 700 1- Bergamo A. Callerio Foundation Onlus, via A. Fleming 22, 34127, Trieste, Italy aut NATIONALLICENCE 773 0- JBIC Journal of Biological Inorganic Chemistry Springer Berlin Heidelberg 20/7(2015-10-01), 1163-1173 0949-8257 20:7<1163 2015 20 775