Reduction of lung metastasis by ImH[trans-RuCl4(DMSO)Im]: mechanism of the selective action investigated on mouse tumors.
NAMI-A (imidazolium trans-imidazoledimethylsulfoxidetetrachlororuthenate, ImH[trans-RuCl4(DMSO)Im]) is a new ruthenium compound active against lung metastasis of solid metastasizing tumors. We have tested this compound in mice with Lewis lung carcinoma or MCa mammary carcinoma in order to compare the effects on primary tumor and lung metastases with possible alterations of cell cycle distribution of tumor cells. We have also investigated whether there were unequal tissue accumulations of the compound itself at different dose levels ranging from 17.5 to 70 mg/kg/day given for six consecutive days. NAMI-A caused a reduction of metastasis weight larger than that of metastasis number; we explain this finding as the capacity of NAMI-A to selectively interfere with the growth of metastases already settled in the lungs. However, this specificity is not simply related to a larger concentration of NAMI-A in the lungs than in other tissues. Following i.p. treatment, NAMI-A rapidly disappeared from the peritoneal cavity; its low blood concentration may be caused by rapid renal clearance. These data provide further evidence for a selective anti-metastasis effect of the ruthenium complex NAMI-A. The reduction of lung metastasis is followed by a significant prolongation of the host's life-time expectancy, indicating a therapeutic benefit of NAMI-A on lung metastases from solid tumors.
Sava
G
G
Callerio Foundation, Institutes of Biological Research, University of Trieste, Italy. gsava@fc.univ.trieste.it
Clerici
K
K
Capozzi
I
I
Cocchietto
M
M
Gagliardi
R
R
Alessio
E
E
Mestroni
G
G
Perbellini
A
A
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy / Q000473:pathology / Q000556:secondary; D002453:Cell Cycle / Q000187:drug effects; D004121:Dimethyl Sulfoxide / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D005260:Female; D005434:Flow Cytometry; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary*; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008815:Mice, Inbred Strains; D009942:Organometallic Compounds / Q000494:pharmacology* / Q000633:toxicity; D012428:Ruthenium / Q000032:analysis / Q000493:pharmacokinetics; D017975:Ruthenium Compounds; D013054:Spectrophotometry, Atomic; D014018:Tissue Distribution
D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D017975:Ruthenium Compounds; C113661:imidazolium-bis(imidazole)dimethylsulfoxideimidazotetrachlororuthenate(III); D012428:Ruthenium; D004121:Dimethyl Sulfoxide