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Antimetastatic action and toxicity on healthy tissues of Na[trans-RuCl4(DMSO)Im] in the mouse

Abstract

The ruthenium-dimethylsulfoxide complex Na(trans-RuCl4(DMSO)Im] was given i.v. to mice bearing MCa mammary carcinoma and its effects on tumor growth and on healthy host tissues were studied by macroscopic examination of primary tumor growth, by survival time, and by histological analysis using light microscopy and SEM. Either by means ofvivo-vivo bioassays or by microscopic examination it appeared that the growth of lung tumors was markedly reduced, whereas the growth of the i.m. primary tumor was much less affected. These effects account for the prolongation of survival time and for the cure rate observed. The favourable effect on survival time was also influenced by the lack of significant cytotoxicity for normal tissues such as lung and kidney epithelia, muscle and liver cells, splenocytes and bone marrow. It thus appears that the selective interaction with tumor cells in the lungs cannot simply be attributed to a selectively higher localization of the compound at this site, nor to a modification of the histological structure of primary tumor. These results highlight the pharmacologic properties of this compound for the control of solid tumor metastases, an effect that was shown to be similarly exerted on advanced tumor metastases.

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References

  1. 1.

    Sava G, Pacor S, Mestroni G and Alessio E, 1992, Effects of the ruthenium(III) complexes [mer-RuCl3(DMSO)2Im]ℴ and Na[trans-RuCl4(DMSO)Im] on solid mouse tumors.Anti-Cancer Drugs,3, 25–31.

  2. 2.

    Sava G, Pacor S, Mestroni G and Alessio E, 1992, Na[trans-RuCl4(DMSO)Im], a metal complex of ruthenium with antimetastatic properties.Clin Exp Metastasis,10, 273–80.

  3. 3.

    Sava G, Pacor S, Bregant F, Ceschia V and Mestroni G, 1990, Metal complexes of ruthenium: antineoplastic properties and perspectives.Anti-Cancer Drugs,1, 99–108.

  4. 4.

    Talmadge JE, 1983, The selective nature of metastasis.Cancer Metastasis Rev,2, 25–40.

  5. 5.

    Heppner GH and Miller BE, 1983, Tumor heterogeneity: biological implications and therapeutic consequences.Cancer Metastasis Rev,2, 5–24.

  6. 6.

    Greig RG and Trainer DL, 1986, Shaping future strategies for the pharmacological control of tumor cell metastases.Cancer Metastasis Rev,5, 3–14.

  7. 7.

    Alessio E, Balducci G, Calligaris M,et al. 1991, Synthesis, molecular structure, and chemical behavior of hydrogen trans-bis(dimethylsulfoxide)tetrachlororuthenate (III) and mer-trichlorotris (dimethylsulfoxide) ruthenium (III): the first fully characterized chloride-dimethylsulfoxide-ruthenium(III) complexes.Inorg Chem,30, 609–18.

  8. 8.

    Poliak-Blazi M, Boranic M, Marzan B, Radacic M, 1981, A transplantable aplastic mammary carcinoma of CBA mice.Vet Arh,51, 99–107.

  9. 9.

    Houghton PJ, Taylor DM, 1977, Fractional incorporation of 3[H]-thymidine and DNA specific activity as assays of inhibition of tumor growth.Brit J Cancer,35, 68–77.

  10. 10.

    Tanabe M and Yamamoto G, 1975,97Ru and103Ru in subcutaneous tumor in rodentsActa Medica Okayama,29, 431–6.

  11. 11.

    Som P, Oster ZH, Matsui K,et al. 1983,97Ru-transferrin uptake in tumors and abscess.Eur J Med,8, 491–4.

  12. 12.

    Waters SL, 1983, Potential medical applications of ruthenium isotopes.Coord Chem Rev,52, 171–82.

  13. 13.

    Srivastava SC, Mausner LF and Clarke MJ. Radioruthenium-labeled compounds for diagnostic tumor imaging. In: Clarke MJ, ed.Progress in Clinical Biochemistry and Medicine—non-platinum metal complexes in cancer chemotherapy, pp. 111–50. Heidelberg: Springer-Verlag, 1989.

  14. 14.

    Clarke MJ. Ruthenium chemistry pertaining to the design of anticancer agents. In: Clarke MJ, ed.Progress in Clinical Biochemistry and Medicine—non-platinum metal complexes in cancer chemotherapy, pp. 25–39. Heidelberg: Springer-Verlag, 1989.

  15. 15.

    Sava G, Zorzet S, Giraldi T, Mestroni G and Zassinovich G, 1984, Antineoplastic activity and toxicity of an organometallic complex of ruthenium(II) in comparison withcis-PDD in mice bearing solid malignant neoplasms.Eur J Cancer Clin Oncol,20, 841–7.

  16. 16.

    Keppler BK, Henn M, Juhal UM,et al. New ruthenium complexes for the treatment of cancer. In: Clark MJ, ed.Progress in Clinical Biochemistry and Medicine—non-platinum metal complexes in cancer chemotherapy, pp. 41–69. Heidelberg: Springer-Verlag, 1989.

  17. 17.

    Grill V, Mallardi F, Zorzet S, Perissin L and Giraldi T, 1987, Morphological analysis of metastatic potential and antimetastatic drug effects in mice bearing two lines of Lewis lung carcinoma.Clin Exp Metastasis,5, 233–44.

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Correspondence to Gianni Sava.

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Gagliardi, R., Sava, G., Pacor, S. et al. Antimetastatic action and toxicity on healthy tissues of Na[trans-RuCl4(DMSO)Im] in the mouse. Clin Exp Metast 12, 93–100 (1994). https://doi.org/10.1007/BF01753975

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Keywords

  • antimetastatic
  • cancer
  • CBA mice
  • histology
  • host toxicity
  • ruthenium complex
  • survival