Na[trans-RuCl4(DMSO)Im], a metal complex of ruthenium with antimetastatic properties.

Abstract

The antitumor and antimetastatic effects of a ruthenium(III) complex, Na[trans-RuCl4(DMSO)Im], have been examined in mice bearing MCa mammary carcinoma. Na[trans-RuCl4(DMSO)Im] is capable of reducing primary tumor growth and of prolonging the survival time with different schedules of administration. However, better effects were obtained (a) with treatments started soon after tumor implantation, (b) with daily administration rather than with treatments at 4-day intervals and (c) using relatively low daily doses. The prolongation of survival time in tumor-bearing hosts, greater than that obtained with cisplatin, cannot be simply related to the effect on primary tumor growth, always less than that of cisplatin. Rather, emphasis is placed on the reduction of lung metastasis formation, obtained either by i.v. injection of tumor cells (lung colonization or spontaneously from i.m. tumor implants, which is significantly greater than the reduction of primary tumor growth. The antimetastatic effect depends on the treatment schedule and is greater with low doses given daily than with high doses administrated with drug-free intervals. Metastasis reduction involved mainly large metastatic nodules, reducing the average weight of each metastasis by 8-fold for spontaneous metastases and by 5-fold for lung colonies. The antimetastatic action of Na[trans-RuCl4(DMSO)Im] thus indicates the possibility that related analogs can represent a new generation of antitumor compounds capable of selectively interacting with metastasis formation of solid tumors.