Table of Contents
Metal-Based Drugs
Volume 2009, Article ID 681270, 9 pages
Research Article

Inhibitory Effects of the Ruthenium Complex KP1019 in Models of Mammary Cancer Cell Migration and Invasion

1Callerio Foundation Onlus, Via A. Fleming 22-31, 34127 Trieste, Italy
2Institute of Inorganic Chemistry, University of Vienna, Waehringer Strasse 42, 1090 Vienna, Austria
3Department of Life Sciences, University of Trieste, Via L. Giorgieri 7, 34127 Trieste, Italy

Received 16 April 2009; Accepted 22 June 2009

Academic Editor: Simon Fricker

Copyright © 2009 A. Bergamo et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. M. J. Clarke, F. Zhu, and D. R. Frasca, “Non-platinum chemotherapeutic metallopharmaceuticals,” Chemical Reviews, vol. 99, no. 9, pp. 2511–2533, 1999. View at Google Scholar
  2. M. J. Clarke, “Ruthenium metallopharmaceuticals,” Coordination Chemistry Reviews, vol. 236, pp. 209–233, 2003. View at Google Scholar
  3. C. G. Hartinger, M. A. Jakupec, S. Zorbas-Seifried et al., “KP1019, a new redox-active anticancer agent-preclinical development and results of a clinical phase I study in tumor patients,” Chemistry and Biodiversity, vol. 5, no. 10, pp. 2140–2155, 2008. View at Publisher · View at Google Scholar · View at PubMed
  4. P. Schluga, C. G. Hartinger, A. Egger et al., “Redox behavior of tumor-inhibiting ruthenium(III) complexes and effects of physiological reductants on their binding to GMP,” Dalton Transactions, vol. 6, no. 14, pp. 1796–1802, 2006. View at Publisher · View at Google Scholar · View at PubMed
  5. B. K. Keppler, M. Henn, U. M. Juhl, M. R. Berger, R. Niebl, and F. E. Wagner, “New ruthenium complexes for the treatment of cancer,” in Progress in Clinical Biochemistry and Medicine, vol. 10, pp. 41–69, Springer, Berlin, Germany, 1989. View at Google Scholar
  6. S. Kapitza, M. Pongratz, M. A. Jakupec et al., “Heterocyclic complexes of ruthenium(III) induce apoptosis in colorectal carcinoma cells,” Journal of Cancer Research and Clinical Oncology, vol. 131, no. 2, pp. 101–110, 2005. View at Publisher · View at Google Scholar · View at PubMed
  7. G. Sava, F. Frausin, M. Cocchietto et al., “Actin-dependent tumour cell adhesion after short-term exposure to the antimetastasis ruthenium complex NAMI-A,” European Journal of Cancer, vol. 40, no. 9, pp. 1383–1396, 2004. View at Publisher · View at Google Scholar · View at PubMed
  8. B. K. Keppler, W. Rupp, U. M. Juhl, H. Endres, R. Niebl, and W. Balzer, “Synthesis, molecular structure, and tumor-inhibiting properties of imidazolium trans-bis(imidazole)tetrachlororuthenate(III) and its methyl-substituted derivatives,” Inorganic Chemistry, vol. 26, no. 26, pp. 4366–4370, 1987. View at Google Scholar
  9. K.-G. Lipponer, E. Vogel, and B. K. Keppler, “Synthesis, characterization and solution chemistry of trans-indazoliumtetrachlorobis(indazole)ruthenate(III), a new anticancer ruthenium complex. IR, UV, NMR, HPLC investigations and antitumor activity. Crystal structures of trans-1-methyl-indazoliumtetrachlorobis-(1-methylindazole) ruthenate(III) and its hydrolysis product trans-monoaquatrichlorobis-(1-methylindazole)-ruthenate(III),” Metal-Based Drugs, vol. 3, no. 5, pp. 243–260, 1996. View at Google Scholar
  10. J. A. Cook and J. B. Mitchell, “Viability measurements in mammalian cell systems,” Analytical Biochemistry, vol. 179, no. 1, pp. 1–7, 1989. View at Google Scholar
  11. P. Skehan, R. Storeng, D. Scudiero et al., “New colorimetric cytotoxicity assay for anticancer-drug screening,” Journal of the National Cancer Institute, vol. 82, no. 13, pp. 1107–1112, 1990. View at Google Scholar
  12. A. Albini, Y. Iwamoto, H. K. Kleinman et al., “A rapid in vitro assay for quantitating the invasive potential of tumor cells,” Cancer Research, vol. 47, no. 12, pp. 3239–3245, 1987. View at Google Scholar
  13. W. Kueng, E. Silber, and U. Eppenberger, “Quantification of cells cultured on 96-well plates,” Analytical Biochemistry, vol. 182, no. 1, pp. 16–19, 1989. View at Google Scholar
  14. M. C. Alley, D. A. Scudiero, A. Monks et al., “Feasibility of drug screening with panels of human tumor cell lines using a microculture tetrazolium assay,” Cancer Research, vol. 48, no. 3, pp. 589–601, 1988. View at Google Scholar
  15. M. M. Bradford, “A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein dye binding,” Analytical Biochemistry, vol. 72, no. 1-2, pp. 248–254, 1976. View at Google Scholar
  16. M. Poliak-Blazi, M. Boranic, R. Marzan, and M. A. Radacic, “A transplantable aplastic mammary carcinoma of CBA mice,” Veterinarski Arhiv, vol. 15, pp. 99–107, 1981. View at Google Scholar
  17. S. Zorzet, A. Bergamo, M. Cocchietto et al., “Lack of in vitro cytotoxicity, associated to increased G2-M cell fraction and inhibition of matrigel invasion, may predict in vivo-selective antimetastasis activity of ruthenium complexes,” Journal of Pharmacology and Experimental Therapeutics, vol. 295, no. 3, pp. 927–933, 2000. View at Google Scholar
  18. E. Alessio, G. Balducci, A. Lutman, G. Mestroni, M. Calligaris, and W. M. Attia, “Synthesis and characterization of two new classes of ruthenium(III)-sulfoxide complexes with nitrogen donor ligands (L): Na[trans-RuCl4(R2SO)(L)] and mer, cis-RuCl3(R2SO)(R2SO)(L). The crystal structure of Na[trans-RuCl4(DMSO)(NH3)] 2DMSO, Na[trans-RuCl4(DMSO)(Im)] H2O, Me2CO (Im=imidazole) and mer, cis-RuCl3(DMSO)(DMSO)(NH3),” Inorganica Chimica Acta, vol. 203, no. 2, pp. 205–217, 1993. View at Google Scholar
  19. S. Kapitza, M. A. Jakupec, M. Uhl, B. K. Keppler, and B. Marian, “The heterocyclic ruthenium(III) complex KP1019 (FFC14A) causes DNA damage and oxidative stress in colorectal tumor cells,” Cancer Letters, vol. 226, no. 2, pp. 115–121, 2005. View at Publisher · View at Google Scholar · View at PubMed
  20. A. R. Folgueras, A. M. Pendás, L. M. Sánchez, and C. López-Otín, “Matrix metalloproteinases in cancer: from new functions to improved inhibition strategies,” International Journal of Developmental Biology, vol. 48, no. 5-6, pp. 411–424, 2004. View at Publisher · View at Google Scholar · View at PubMed
  21. C. M. Overall and O. Kleifeld, “Validating matrix metalloproteinases as drug targets and anti-targets for cancer therapy,” Nature Reviews Cancer, vol. 6, no. 3, pp. 227–239, 2006. View at Publisher · View at Google Scholar · View at PubMed
  22. E. Alessio, G. Mestroni, A. Bergamo, and G. Sava, “Ruthenium anticancer drugs,” in Metal Ions in Biological Systems; Metal Complexes in Tumor Diagnosis and as Anticancer Agents, A. Sigel and H. Sigel, Eds., vol. 42, pp. 323–351, Marcel Dekker, New York, NY, USA, 2004. View at Google Scholar
  23. A. Bergamo, A. Masi, P. J. Dyson, and G. Sava, “Modulation of the metastatic progression of breast cancer with an organometallic ruthenium compound,” International Journal of Oncology, vol. 33, no. 6, pp. 1281–1289, 2008. View at Publisher · View at Google Scholar