title: Tumour cell uptake of the metastasis inhibitor ruthenium complex NAMI-A and its in vitro effects on KB cells.
abstract: OBJECTIVE
  The uptake of NAMI-A (imidazolium trans-imidazoledimethylsulphoxidetetrachlororuthenate) 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 degrees 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 dependent 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.
authors.affiliation: Callerio Foundation Onlus, via A. Fleming 22-31, 34127-Trieste, Italy.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Frausin
authors.forename: Moreno
authors.initials: M
authors.lastname: Cocchietto
authors.forename: Alberta
authors.initials: A
authors.lastname: Bergamo
authors.forename: Vito
authors.initials: V
authors.lastname: Scarcia
authors.forename: Ariella
authors.initials: A
authors.lastname: Furlani
authors.forename: Gianni
authors.initials: G
authors.lastname: Sava
mesh_terms: D000596:Amino Acids / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D001693:Biological Transport, Active / Q000187:drug effects; D002021:Buffers; D002118:Calcium / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D003470:Culture Media / Q000494:pharmacology; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004058:Diffusion; D004121:Dimethyl Sulfoxide / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D007624:KB Cells / Q000187:drug effects* / Q000378:metabolism; D008274:Magnesium / Q000494:pharmacology; D009942:Organometallic Compounds / Q000378:metabolism / Q000494:pharmacology*; D011339:Probenecid / Q000494:pharmacology; D017975:Ruthenium Compounds; D012996:Solutions; D013054:Spectrophotometry, Atomic
chemical_list: D000596:Amino Acids; D000970:Antineoplastic Agents; D002021:Buffers; D003470:Culture Media; D016895:Culture Media, Serum-Free; D009942:Organometallic Compounds; D017975:Ruthenium Compounds; D012996:Solutions; C113661:imidazolium-bis(imidazole)dimethylsulfoxideimidazotetrachlororuthenate(III); D008274:Magnesium; D011339:Probenecid; D002118:Calcium; D004121:Dimethyl Sulfoxide