Actin-dependent tumour cell adhesion after short-term exposure to the antimetastasis ruthenium complex NAMI-A

Sava, Gianni; Frausin, Fabiana; Cocchietto, Moreno; Vita, Francesca; Podda, Elena; Spessotto, Paola; Furlani, A.; Scarcia, V.; Zabucchi, Giuliano

doi:10.1016/j.ejca.2004.01.034

Cited by 78 publications

(67 citation statements)

References 26 publications

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“…Metastasis control: a) limiting actin dependent adhesion in vitro [26,27]; b) limiting in vitro tumor cell motility by cytoskeleton remodeling: activation of collagen receptor integrin β1 on the cell surface results in RhoA activation and subsequently to rearrangement of the cytoskeleton in vitro. [23,[26][27][28]; c) anti-invasive effect in vitro and in vivo by promoting capsule formation: NAMI-A increases the extracellular matrix around tumor cells and tumor vasculature by triggering fibrotic reactions, regulates TGFβ1 expression, binds to collagen and stimulates collagen production.…”

Section: Nami-amentioning

confidence: 99%

Phase I/II study with ruthenium compound NAMI-A and gemcitabine in patients with non-small cell lung cancer after first line therapy

et al. 2014

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Section: Nami-amentioning

confidence: 99%

Phase I/II study with ruthenium compound NAMI-A and gemcitabine in patients with non-small cell lung cancer after first line therapy

et al. 2014

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“…In general, data on the mechanism of action of NAMI-A seem to exclude DNA as the primary target for its activity on metastases (15)(16)(17), and binding to DNA is far weaker than that of platinum complexes (18). Conversely, NAMI-A was shown to bind tightly to serum albumin and serum transferrin, two representative plasma proteins (19,20), suggesting that binding to specific proteins may represent the molecular basis for its peculiar biological activity.…”

Section: Introductionmentioning

confidence: 99%

The role of cisplatin and NAMI-A plasma-protein interactions in relation to combination therapy

Khalaila¹,

Bergamo²,

Bussy³

et al. 2006

Int J Oncol

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Abstract. The aim of the study is to evaluate the differences of protein binding of NAMI-A, a new ruthenium drug endowed with selective antimetastatic properties, and of cisplatin and to ascertain the possibility to use two drugs based on heavy metals in combination to treat solid tumour metastases. For this purpose, we have developed a technique that allows the proteins, to which metal drugs bind, to be identified from real protein mixtures. Following incubation with the drugs, the bands containing platinum and/or ruthenium are separated by native PAGE, SDS-PAGE and 2D gel electrophoresis, and identified using laser ablation inductively coupled plasma mass spectrometry. Both drugs interact with essentially the same proteins which, characterised by proteomics, are human serum albumin precursor, macroglobulin ·2 and human serotransferrin precursor. The interactions of NAMI-A are largely reversible whereas cisplatin forms stronger interactions that are less reversible. These data correlate well with the MCa mammary carcinoma model on which full doses of NAMI-A combined with cisplatin show additive effects as compared to each treatment taken alone, independently of whether NAMI-A precedes or follows cisplatin. Furthermore, the implication from this study is that the significantly lower toxicity of NAMI-A, compared to cisplatin, could be a consequence of differences in the mode of binding to plasma proteins, involving weaker interactions compared to cisplatin.

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“…Imidazolium trans-imidazole dimethyl sulfoxide tetrachlororuthenate (DMSO)(im)], NAMI-A, im ϭ imidazole], is a ruthenium compound endowed in vitro with proadhesive effects (Bergamo et al, 2000;Sava et al, 2004) that has recently completed a phase I clinical trial at the Netherlands Cancer Institute (Rademaker-Lakhai et al, 2004). The effect on cell adhesion, as well as the capacity to inhibit angiogenesis and matrix metalloproteinases (Vacca et al, 2002), has been suggested to be responsible for in vivo NAMI-A activity on lung metastases of a number of solid tumors (Sava et al, 1998Bergamo et al, 1999).…”

mentioning

confidence: 99%

Free Exchange across Cells, and Echistatin-Sensitive Membrane Target for the Metastasis Inhibitor NAMI-A (Imidazoliumtrans-Imidazole Dimethyl Sulfoxide Tetrachlororuthenate) on KB Tumor Cells

Frausin¹,

Scarcia²,

Cocchietto³

et al. 2004

J Pharmacol Exp Ther

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The duration of cell proadhesive effects induced by imidazolium trans-imidazole dimethyl sulfoxide tetrachlororuthenate (NAMI-A), a compound endowed with in vivo antimetastatic properties, was tested in vitro on the human epithelial tumor cell line KB. The intensity of proadhesive effects continues to increase up to 48 to 72 h after NAMI-A withdrawal and declines only after 96 h. The proadhesive effect on cells seeded on fibronectin is greater than on plastic, since it already reaches its maximum after 24 h. This effect suggests a role for integrin activation, which is further stressed by the inhibitory activity of the disintegrin molecule echistatin. The intensity and duration of NAMI-A's proadhesive effects are correlated to cell exposure time and to the rapid release of NAMI-A metabolites in the culture medium in the first 5 min after drug withdrawal. These metabolites are probably neutral species with ruthenium-bound bioligands to allow for the rapid exchange between cells and extracellular medium. These data suggest a long-lasting effect of NAMI-A in biological systems, even at very low concentrations, and stress the low and reversible effects on kidney, where it naturally concentrates. These data on proadhesive effects are, further, relevant for in vivo antimetastatic effects, as this adhesion is associated to cell motility and invasion, which in turn are related to tumor malignancy and metastasis.

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Actin-dependent tumour cell adhesion after short-term exposure to the antimetastasis ruthenium complex NAMI-A

Cited by 78 publications

References 26 publications

Phase I/II study with ruthenium compound NAMI-A and gemcitabine in patients with non-small cell lung cancer after first line therapy

Phase I/II study with ruthenium compound NAMI-A and gemcitabine in patients with non-small cell lung cancer after first line therapy

The role of cisplatin and NAMI-A plasma-protein interactions in relation to combination therapy

Free Exchange across Cells, and Echistatin-Sensitive Membrane Target for the Metastasis Inhibitor NAMI-A (Imidazoliumtrans-Imidazole Dimethyl Sulfoxide Tetrachlororuthenate) on KB Tumor Cells

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