Effects of the Ru(III) complexes [mer-RuCl3(DMSO)2Im]degrees and Na[trans-RuCl4(DMSO)Im] on solid mouse tumors.
The effects of two new Ru(III) complexes, [mer-RuCl3(DMSO)2Im] degrees and Na[trans-RuCl4(DMSO)Im], 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)Im] 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)2Im]degrees 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)2Im]degrees) or for stabilizing the compound in the solution before injection (i.e. Na[trans-RuCl4(DMSO)Im]), reduces the anti-tumor potency. Conversely, the antitumor effects of Na[trans-RuCl4(DMSO)Im] are more pronounced in mice hydrated with isotonic saline. We conclude that Na[trans-RuCl4(DMSO)Im] 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.
Sava
G
G
Institute of Pharmacology, School of Pharmacy, University of Trieste, Italy.
Pacor
S
S
Mestroni
G
G
Alessio
E
E
D000818:Animals; D002277:Carcinoma / Q000188:drug therapy*; D002945:Cisplatin / Q000627:therapeutic use; D004121:Dimethyl Sulfoxide / Q000031:analogs & derivatives* / Q000494:pharmacology; D004304:Dosage Forms; D004334:Drug Administration Schedule; D004354:Drug Screening Assays, Antitumor; D005260:Female; D008175:Lung Neoplasms / Q000188:drug therapy*; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy*; D008546:Melanoma, Experimental / Q000188:drug therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D009942:Organometallic Compounds / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D004304:Dosage Forms; D009942:Organometallic Compounds; C075498:dimethylsulfoxideimidazoletetrachlororuthenate(III); C075497:trichlorobis(dimethylsulfoxide)imidazoleruthenium(III); D002945:Cisplatin; D004121:Dimethyl Sulfoxide