IN-VITRO CYTOSTATIC ACTIVITY AND DNA-INTERACTION OF THE NEW LIVER ORGANOTROPIC COMPLEX CHLORO-BIS-CHOLYLGLYCINATE-PLATINUM(II)

Background: The liver organotropic properties of the new bioinorganic complex of platinum(II) and glycocholic acid, Bamet-H2 have been repor ted previously. The aim of this work was to investigate the in vitro c ytostatic activity of this compound Materials and Methods: The inhibit ion of cell growth and DNA synthesis by mouse leukemia L-1210 (mL), mo use hepatoma Hepa 1-6 (mH), rat hepatoma McA-RH7777 (rH) and human col on adenocarcinoma LS-174T (hCC) cells were measured. The effects on th e electrophoretic mobility of the pUC18 plasmid, the DNA denaturation temperature and ethidium bromide (EthBr) binding to DNA were studied. Results: A significant antiproliferative effect for Bamet-H2 was found (mH similar to hCC > mL similar to rH). DNA synthesis was also marked ly inhibited (mH similar to hCC similar to mL similar to rH). Bamet-H2 -induced a change in the electrophoretic mobility of pUC18 and the inc rease in DNA denaturation temperature suggested the existence of DNA-B amet-H2 interactions. Scatchard plots obtained from EthBr displacement assays revealed that Bamet H2 induces a reduction in both the number of DNA sites available and their ability to bind EthBr. Conclusion: Ba met H2 is able to interact with DNA, inhibit DNA synthesis, and hence reduce cell proliferation.