The
ruthenium complexes trans-dichlorotetrakisdimethylsulfoxide
ruthenium(II) (
trans-Ru), imidazolium trans-imidazoletetrachlororuthenate (ICR),
sodium trans-tetramethylensulfoxideisoquinolinetetrachlororuthenate (TEQU), and imidazolium trans-imidazoledimethylsulfoxidetetrachlororuthenate (
NAMI-A) are tested in vitro by short exposure of MCF-7, LoVo, KB, and TS/A
tumor cells to 10(-4) M concentration, and in vivo on
Lewis lung carcinoma by a daily i.p. treatment for 6 consecutive days using equitoxic and maximum tolerated doses.
NAMI-A 1) inhibited
tumor cell invasion of
matrigel, 2) induced a transient accumulation of cells in the G(2)-M phase, 3) did not modify in vitro cell growth, and 4) markedly reduced lung
metastasis formation. TEQU showed significant cytotoxicity in vitro and was not antimetastatic in vivo. ICR and
trans-Ru did not modify cell cycle distribution of in vitro
tumor cells nor did they inhibit
matrigel invasion; ICR was also devoid of antimetastasis effects in vivo.
Ruthenium uptake by
tumor cells did account for in vitro cytotoxicity but not for other in vitro actions or for in vivo antimetastasis activity. The contemporary absence of cytotoxicity, associated to inhibition of
matrigel crossing and to transient block in the premitotic G(2)-M phase, appears to be prerequisites for a
ruthenium compound to show in vivo-selective antimetastasis effect. The validation of this model for other classes of compounds will allow an understanding of the combined weight of the above-mentioned phenomena for
tumor metastasis growth and control.