PT - JOURNAL ARTICLE AU - A. Bergamo AU - R. Gagliardi AU - V. Scarcia AU - A. Furlani AU - E. Alessio AU - G. Mestroni AU - G. Sava TI - In Vitro Cell Cycle Arrest, In Vivo Action on Solid Metastasizing Tumors, and Host Toxicity of the Antimetastatic Drug NAMI-A and Cisplatin DP - 1999 Apr 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 559--564 VI - 289 IP - 1 4099 - http://jpet.aspetjournals.org/content/289/1/559.short 4100 - http://jpet.aspetjournals.org/content/289/1/559.full SO - J Pharmacol Exp Ther1999 Apr 01; 289 AB - The effects of NAMI-A (imidazoliumtrans-imidazoledimethyl sulfoxide-tetrachlororuthenate) are compared with cisplatin on tumor cells cultured in vitro at doses of 1 to 100 μM and on tumor metastases in vivo at maximum tolerated doses. Using mouse tumors that metastasize to the lungs, NAMI-A given i.p. for 6 consecutive days at 35 mg/kg/day, was effective independently of the tumor line being treated and of the stage of metastasis growth. Conversely, cisplatin (2 mg/kg/day for 6 days) was as effective as NAMI-A on MCa mammary carcinoma and TS/A adenocarcinoma and less effective than NAMI-A on Lewis lung carcinoma. Cisplatin reduced body weight gain and spleen weight during treatment and was much more toxic than NAMI-A on liver sinusoids, kidney tubules, and lung epithelium. In vitro NAMI-A caused a transient cell cycle arrest of tumor cells in the premitotic G2/M phase, whereas cisplatin caused a progressive dose-dependent disruption of cell cycle phases. Correspondingly, NAMI-A did not modify cell growth, whereas cisplatin caused a dose-dependent reduction of cell proliferation, as determined by sulforhodamine B test. Thus, NAMI-A, unlike cisplatin, is a potent agent for the treatment of solid tumor metastases as well as when these tumor lesions are in an advanced stage of growth. NAMI-A is endowed with a mechanism of action unrelated to direct tumor cell cytotoxicity, and such mechanism of action is responsible for a reduced host toxicity. The American Society for Pharmacology and Experimental Therapeutics