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Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on December 3, 2004; DOI: 10.1124/jpet.104.078352

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Fabiana Frausin
Vito Scarcia
Ariella Furlani
Barbara Serli
Enzo Alessio
Gianni Sava
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Received for publication September 27, 2004.
Revised December 2, 2004.
Accepted for publication December 2, 2004.

FREE EXCHANGE ACROSS CELLS, AND ECHISTATIN-SENSITIVE MEMBRANE TARGET FOR THE METASTASIS INHIBITOR NAMI-A ON KB TUMOR CELLS

Fabiana Frausin 1, Vito Scarcia 1, Moreno Cocchietto 2, Ariella Furlani 1, Barbara Serli 1, Enzo Alessio 1, Gianni Sava 2*

1 University of Trieste 2 Callerio Foundation Onlus

* Address correspondence to: E-mail: g.sava{at}callerio.org

Abstract

The duration of cell pro-adhesive effects induced by imidazolium trans-imidazole dimethylsulfoxidetetrachlororuthenate (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 pro-adhesive effects continues to increase up to 48-72 h after NAMI-A withdrawal, and declines only after 96 h. The pro-adhesive effect on cells seeded on fibronectin is greater than on plastic, as it reaches its maximum already after 24 h. This effect suggests a role for integrins activation, which is further stressed by the inhibitory activity of the disintegrin molecule echistatin. The intensity and duration of NAMI-A's pro-adhesive effects are correlated to cell exposure time, and to the rapid release of NAMI-A's 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 pro-adhesive 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.


Key words: ADHESION, CELL, INTEGRIN, METABOLISM, RUTHENIUM, TUMOR


This article has been cited by other articles:


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B. Gava, S. Zorzet, P. Spessotto, M. Cocchietto, and G. Sava
Inhibition of B16 Melanoma Metastases with the Ruthenium Complex Imidazolium trans-Imidazoledimethylsulfoxide-tetrachlororuthenate and Down-Regulation of Tumor Cell Invasion
J. Pharmacol. Exp. Ther., April 1, 2006; 317(1): 284 - 291.
[Abstract] [Full Text] [PDF]


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