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Effects of the Ruthenium-Based Drug NAMI-A on the Roles Played by TGF-β1 in the Metastatic Process

Effects of the Ruthenium-Based Drug NAMI-A on the Roles Played by TGF-β1 in the Metastatic Process

L Brescacin, A Masi, G Sava, A Bergamo

J Biol Inorg Chem. 2015 Oct;20(7):1163-73.

PMID: 26369538

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP201653761	NAMI-A		201653-76-1	Price

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