Effects of the ruthenium-based drug NAMI-A on the roles played by TGF-β1 in the metastatic process

Verfasser / Beitragende:
[L. Brescacin, A. Masi, G. Sava, A. Bergamo]
Ort, Verlag, Jahr:
2015
Enthalten in:
JBIC Journal of Biological Inorganic Chemistry, 20/7(2015-10-01), 1163-1173
Format:
Artikel (online)
ID: 605507139
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024 7 0 |a 10.1007/s00775-015-1297-8  |2 doi 
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245 0 0 |a Effects of the ruthenium-based drug NAMI-A on the roles played by TGF-β1 in the metastatic process  |h [Elektronische Daten]  |c [L. Brescacin, A. Masi, G. Sava, A. Bergamo] 
520 3 |a 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: 
540 |a SBIC, 2015 
690 7 |a Anticancer drug  |2 nationallicence 
690 7 |a Heavy metal  |2 nationallicence 
690 7 |a Biomedicine  |2 nationallicence 
690 7 |a Molecular dynamics  |2 nationallicence 
690 7 |a BSA : Bovine serum albumin  |2 nationallicence 
690 7 |a CHK1 : Checkpoint kinase 1  |2 nationallicence 
690 7 |a CMF-DPBS : Calcium and Magnesium Free Dulbecco's Phosphate Buffered Saline  |2 nationallicence 
690 7 |a ECM : Extracellular matrix  |2 nationallicence 
690 7 |a DMEM : Dulbecco's modified Eagle's medium  |2 nationallicence 
690 7 |a DPBS : Dulbecco's Phosphate Buffered Saline  |2 nationallicence 
690 7 |a FBS : Foetal bovine serum  |2 nationallicence 
690 7 |a GRP78 : 78kDa glucose-regulated protein  |2 nationallicence 
690 7 |a LB : Lysis buffer  |2 nationallicence 
690 7 |a MMPs : Matrix metallo proteinases  |2 nationallicence 
690 7 |a NAMI-A : Imidazolium trans-imidazoletetrachlororuthenate  |2 nationallicence 
690 7 |a ROS : Reactive oxygen species  |2 nationallicence 
690 7 |a SRB : Sulforhodamine B  |2 nationallicence 
690 7 |a TCA : Trichloro acetic acid  |2 nationallicence 
690 7 |a TGF-β1 : Transforming growth factor beta 1  |2 nationallicence 
690 7 |a TIMPs : Tissue inhibitors of MMPs  |2 nationallicence 
690 7 |a TMB : 3,3′,5,5′-Tetramethylbenzidine  |2 nationallicence 
700 1 |a Brescacin  |D L.  |u Callerio Foundation Onlus, via A. Fleming 22, 34127, Trieste, Italy  |4 aut 
700 1 |a Masi  |D A.  |u Callerio Foundation Onlus, via A. Fleming 22, 34127, Trieste, Italy  |4 aut 
700 1 |a Sava  |D G.  |u Callerio Foundation Onlus, via A. Fleming 22, 34127, Trieste, Italy  |4 aut 
700 1 |a Bergamo  |D A.  |u Callerio Foundation Onlus, via A. Fleming 22, 34127, Trieste, Italy  |4 aut 
773 0 |t JBIC Journal of Biological Inorganic Chemistry  |d Springer Berlin Heidelberg  |g 20/7(2015-10-01), 1163-1173  |x 0949-8257  |q 20:7<1163  |1 2015  |2 20  |o 775 
856 4 0 |u https://doi.org/10.1007/s00775-015-1297-8  |q text/html  |z Onlinezugriff via DOI 
898 |a BK010053  |b XK010053  |c XK010000 
900 7 |a Metadata rights reserved  |b Springer special CC-BY-NC licence  |2 nationallicence 
908 |D 1  |a research-article  |2 jats 
949 |B NATIONALLICENCE  |F NATIONALLICENCE  |b NL-springer 
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950 |B NATIONALLICENCE  |P 700  |E 1-  |a Brescacin  |D L.  |u Callerio Foundation Onlus, via A. Fleming 22, 34127, Trieste, Italy  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Masi  |D A.  |u Callerio Foundation Onlus, via A. Fleming 22, 34127, Trieste, Italy  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Sava  |D G.  |u Callerio Foundation Onlus, via A. Fleming 22, 34127, Trieste, Italy  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Bergamo  |D A.  |u Callerio Foundation Onlus, via A. Fleming 22, 34127, Trieste, Italy  |4 aut 
950 |B NATIONALLICENCE  |P 773  |E 0-  |t JBIC Journal of Biological Inorganic Chemistry  |d Springer Berlin Heidelberg  |g 20/7(2015-10-01), 1163-1173  |x 0949-8257  |q 20:7<1163  |1 2015  |2 20  |o 775