Tumour cell uptake of the metastasis inhibitor ruthenium complex NAMI-A and its in vitro effects on KB cells

Purpose: The uptake of NAMI-A (imidazoli- um trans-imidazoledimethylsulphoxidetetrachlororuthe- nate) by KB cells in vitro was compared with the effects of this compound on the cell cycle phase distribution of the cells. Methods: NAMI-A uptake was determined by flameless atomic absorption spectroscopy, and the cell cycle phase distribution was determined by flow cytometry. Results: NAMI-A uptake was proportional to its concentration in the incubation medium. The use of a number of incubation conditions showed that NAMI-A uptake from MEM was independent of the presence of serum and dependent on the presence of amino acids in the incubation medium, and that NAMI- A uptake was markedly higher when the cells were incubated in PBS. The uptake increase observed in PBS did not occur when the cells were kept at 0-4� C, suggesting the presence of active transportation of NAMI-A into cells. In addition, the presence of divalent cations such as Ca 2+ and Mg 2+ , appeared to facilitate NAMI-A uptake. The anionic substance transport inhibitor probenecid significantly reduced the active transportation of NAMI-A into cells. The effects of NAMI-A on cell cycle distribution were strictly depen- dent on its uptake by tumour cells and not on its extracellular concentration. Conclusions: These findings suggest the interaction of NAMI-A with biological components resulting in possible consequences for the distribution of the compound itself. Furthermore, NAMI-A enters tumour cells both by passive diffusion and by active transportation.