Effects of NAMI-A and some related ruthenium complexes on cell viability after short exposure of tumor cells

A series of three ruthenium complexes, i.e. trans-dichlorotetrakisdimethyl- sulfoxide ruthenium(II) (trans-Ru), imidazolium trans-imidazoletetra-chloro ruthenate (ICR) and sodium trans-tetramethylensulfoxideisoquinoline-tetrach lororuthenate (TEQU), were studied in vitro in comparison to NAMI-A, a pote nt ruthenium-based antimetastasis agent. In vitro challenge of TS/A adenoca rcinoma or KB oral carcinoma tumor cells with 10(-4) M concentration for 1 h evidenced the lack of cytotoxicity of NAMI-A, ICR and trans-Ru, the accum ulation of cells in the G(2)/M pre-mitotic cell phase by NAMI-A and the att achment of tumor cells to the plastic substrate was significantly greater f or NAMI-A than for ICR. These data stress that in vitro cytotoxicity is not necessary for in vivo activity of ruthenium antitumor complexes: NAMI-A, I CR and trans-Ru, are in fact known to be active against murine tumors in th e mouse system. Rather, TEQU, the compound free of in vivo activity, was th e only one to reduce cell growth of In vitro cultured cells. In conclusion, the data on the effects of NAMI-A on in vitro cultured cells show that the increase of cell adhesion properties and the transient cell cycle arrest i n the G(2)/M phase are much more relevant than the effects on cell properti es relevant to cell growth (i.e. on CD44, CD54 or CD71 antigens) for determ ining in vivo antimetastasis activity. [(C) 2000 Lippincott Williams & Wilk ins.].