Reduction of in vivo lung metastases by dinuclear ruthenium complexes is coupled to inhibition of in vitro tumour invasion

  • Authors:
    • Alberta Bergamo
    • Gabriele Stocco
    • Claudia Casarsa
    • Moreno Cocchietto
    • Enzo Alessio
    • Barbara Serli
    • Sonia Zorzet
    • Gianni Sava
  • View Affiliations

  • Published online on: February 1, 2004     https://doi.org/10.3892/ijo.24.2.373
  • Pages: 373-379
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Abstract

Mononuclear ruthenium-dmso compounds showed interesting antimetastatic properties on experimental models of solid tumours. In line with the interesting results with multinuclear platinum complexes, which proved to overcome cisplatin resistance, we thought it worthwhile to test the pharmacological properties of some dinuclear ruthenium complexes to ascertain the possible advantages due to the introduction of a second metal centre over NAMI-A and its mononuclear analogues. These compounds belong to the general formula X2[{RuCl4(dmso-S)}2(μ-L)] or [X][{RuCl4(dmso-S)}(μ-L){RuCl3(dmso-S)(dmso-O)}] where L is a nitrogen donor ligand (pyrazine; pyrimidine; 4,4'-bipyridine; 1,2-bis(4-pyridyl)ethane; 1,2-bis(4-pyridyl) ethylene; 1,3-bis(4-pyridyl)propane) and X a counterion. We focused on parameters related to metastatic ability such as gelatinase activity, detected by zymography, and invasive potential, measured by means of a transwell chamber. These activities were correlated to the ability to inhibit tumour metastases in vivo. All dinuclear complexes, except compound D8 ([NH4]2[{RuCl4(dmso-S)}2(μ-pyz]), decrease the number of tumour cells that cross a matrigel barrier, and inhibit MMP-9 gelatinolytic activity at concentrations lower than that of NAMI-A and of other mononuclear ruthenium complexes. In vivo compounds D5 (Na2[{RuCl4(dmso-S)}2(μ-ethylbipy)]) and D7 ([NH4][{RuCl4(dmso-S)}(μ-pyz){RuCl3(dmso-S) (dmso-O)}]) show anti-metastasis activity, at two dose levels, with mild or null effect on primary tumour growth; compound D8 is the weakest active. All compounds tend to accumulate in liver and kidneys, rather than in tumour and lungs. However, compound D5, the most active in vitro on invasion and gelatinases and active in vivo on metastasis, is better concentrated in the lungs than compound D8 which is less active or inactive in vitro and in vivo. Histological analysis show liver, as well as kidney toxicities that limit in vivo activity. These data thus suggest dinuclear ruthenium complexes as promising anti-invasive agents for cancer treatment.

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February 2004
Volume 24 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Bergamo A, Stocco G, Casarsa C, Cocchietto M, Alessio E, Serli B, Zorzet S and Sava G: Reduction of in vivo lung metastases by dinuclear ruthenium complexes is coupled to inhibition of in vitro tumour invasion. Int J Oncol 24: 373-379, 2004
APA
Bergamo, A., Stocco, G., Casarsa, C., Cocchietto, M., Alessio, E., Serli, B. ... Sava, G. (2004). Reduction of in vivo lung metastases by dinuclear ruthenium complexes is coupled to inhibition of in vitro tumour invasion. International Journal of Oncology, 24, 373-379. https://doi.org/10.3892/ijo.24.2.373
MLA
Bergamo, A., Stocco, G., Casarsa, C., Cocchietto, M., Alessio, E., Serli, B., Zorzet, S., Sava, G."Reduction of in vivo lung metastases by dinuclear ruthenium complexes is coupled to inhibition of in vitro tumour invasion". International Journal of Oncology 24.2 (2004): 373-379.
Chicago
Bergamo, A., Stocco, G., Casarsa, C., Cocchietto, M., Alessio, E., Serli, B., Zorzet, S., Sava, G."Reduction of in vivo lung metastases by dinuclear ruthenium complexes is coupled to inhibition of in vitro tumour invasion". International Journal of Oncology 24, no. 2 (2004): 373-379. https://doi.org/10.3892/ijo.24.2.373