EFFECTS OF RUTHENIUM COMPLEXES ON EXPERIMENTAL-TUMORS - IRRELEVANCE OF CYTOTOXICITY FOR METASTASIS INHIBITION

A series of Ig ruthenium(III) complexes, structurally related to the s elective antimetastatic drug Na[trans-RuCl4(DMSO)Im], and characterize d by the presence of sulfoxide and nitrogen-donor ligands were tested on TLXS lymphoma and some of them on MCa mammary carcinoma to evaluate the dependence of the degree of cytotoxicity and of antimetastatic ac tivity pn the chemical properties. In vitro cytotoxicity is present on ly at high concentrations (>10(-4) M), depends upon lipophilicity and is markedly affected by the presence of 5% serum or plasma samples in the culture medium. The comparison of the effects on in vitro cytotoxi city with in vivo antitumor and antimetastatic action points out that these compounds reduce metastasis formation by a mechanism unrelated t o a direct tumor cell cytotoxicity. If on one hand Na[trans-RuCl4(TMSO )Iq], the compound that shows the most potent in vitro cytotoxic effec ts, is the least effective against metastases, on the other Na[trans-R uCl4-(DMSO)Im], the compound that better reduces metastasis formation, is rather devoid of cytotoxic effects on tumor cells kept in vitro. I n particular, Na[trans-RuCl4(DMSO)Im] seems to distinguish between art ificially induced metastases and spontaneous metastases and reduces on ly the former by a cytotoxic mechanism. Out of all the tested compound s, with the exception of Na[trans-RuCl4(DMSO)Ox], Na[trans-RuCl4(DMSO) Im] is confirmed to be the most selective antimetastatic agent of the group.