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Effects of the Ru(III) complexes [mer-RuCl3(DMSO)2Im]° and Na[trans-RuCl4(DMSO)Im] on solid mouse tumors

1992; Lippincott Williams & Wilkins; Volume: 3; Issue: 1 Linguagem: Inglês

10.1097/00001813-199202000-00005

1473-5741

Gianni Sava, Sabrina Pacor, G. Mestroni, Enzo Alessio,

Asymmetric Hydrogenation and Catalysis

The effects of two new Ru(III) complexes, [mer-RuCl3(DMSO)2lm]° and Na[trans-RuCl4(DMSO)lm], were investigated on primary tumor growth and on the survival time using three solid metastasizing tumors of the mouse: Lewis lung carcinoma, B16 melanoma and MCa mammary carcinoma. Na[trans-RuCl4(DMSO)lm] appears to be the most promising compound, in that: (1) it is soluble in water and therefore easy to handle in comparison with the neutral species [mer-RuCl3(DMSO)2lm]° or to the already described BBR2382; (2) similarly to cisplatin, though at a lower level, it reduces tumor growth in its primary site in each tumor model employed; (3) unlike cisplatin, it increases the life span of tumor-bearing hosts in all tumors used, independently of the effects on primary tumor growth; and (4) it is also effective in reducing spontaneous metastasis formation when the effects on primary tumor growth are completely absent. Dimethylsulfoxide (DMSO), used for solubilizing poorly water-soluble compounds (i.e. [mer- RuCl3(DMSO)2lm]°) or for stabilizing the compound in the solution before injection (i.e. Na[trans-RuCl4(DMSO)lm]), reduces the anti-tumor potency. Conversely, the antitumor effects of Na[trans-RuCl4(DMSO)lm] are more pronounced in mice hydrated with isotonic saline. We conclude that Na[trans-RuCl4(DMSO)lm] is a good candidate for further investigations aimed at ascertaining the mechanism of the anti-metastatic activity and of the positive effects on survival time of mice bearing solid metastasizing tumors.