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: L Brescacin, A Masi, G Sava, A Bergamo
• Journal: Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry (J Biol Inorg Chem) Vol. 20 Issue 7 Pg. 1163-73 (Oct 2015) ISSN: 1432-1327 [Electronic] Germany
• PMID: 26369538 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Organometallic Compounds
• Ruthenium Compounds
• Transforming Growth Factor beta1
• imidazolium-bis(imidazole)dimethylsulfoxideimidazotetrachlororuthenate(III)
• Ruthenium
• Dimethyl Sulfoxide

Topics

• Antineoplastic Agents (chemistry, pharmacology)
• Cell Adhesion (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Dimethyl Sulfoxide (analogs & derivatives, chemistry, pharmacokinetics, pharmacology)
• Humans
• Molecular Structure
• Neoplasm Metastasis (drug therapy)
• Neoplasms (drug therapy, physiopathology)
• Organometallic Compounds (chemistry, pharmacokinetics, pharmacology)
• Ruthenium (chemistry, pharmacology)
• Ruthenium Compounds
• Transforming Growth Factor beta1 (metabolism)