Sava G, Pacor S, Zorzet S, Alessio E, Mestroni G
Institute of Pharmacology, Faculty of Pharmacy, University of Trieste, Italy.
Pharmacol Res. 1989 Sep-Oct;21(5):617-28. doi: 10.1016/1043-6618(89)90204-1.
The antitumour effects of some ruthenium (II) complexes were tested in mice bearing the solid metastasizing tumour, Lewis lung carcinoma. The toxicity of trans-RuCl2 (DMSO)4 is 10-fold higher than that of its cis-isomer. Qualitatively the antitumour activity of these two complexes is comparable, although trans-isomer is more potent. Both exhibit only marginal effects on primary tumour growth while significantly lowering lung metastasis formation. The effects of trans-RuCl2 (DMSO)4 on primary tumour depend on the inoculum size, being more pronounced with low tumour inocula; significant antitumour effects can be achieved also by replacing Cl with I in the molecule. trans-RuCl2(DMSO)4 markedly reduces the number of lung metastases and particularly their volume; the reduction is comparable to that obtained with equitoxic treatments of cisplatin. Treatment with trans-RuCl2(DMSO)4 for 10 consecutive days, after surgical amputation of primary tumour, significantly prolongs the survival time of the treated mice; cisplatin, at equitoxic doses, is less effective. These data show that dimethylsulphoxide ruthenium(II) complexes possess a significant antitumour and antimetastatic activity in the Lewis lung system, also exhibiting an interesting therapeutic potential when combined with surgical amputation of the primary tumour.