Cyto/genotoxicity evaluation of promising antileukaemic palladium-based drugs

Polyoxometalates (POMs) are discrete, negatively charged metal-oxo clusters of early transition metal ions in high oxidation states. Their biological significance has greatly increased in recent years because of their approved anticancer, antibiotic, and antidiabetic properties. However, toxicity studies have reported adverse effects after in vivo POM studies, which limits their potential application in biomedicine. The aim of this study is to evaluate the in vitro cyto- and genotoxic properties of two polyoxopalladates(II) containing tetravalent metal ion guests, SnPd12 and PbPd12, that were found to possess potent antitumor activities against the human acute promyelocytic cell line HL-60. For this purpose, blood samples obtained from a healthy female donor were treated with three different concentrations (12.5, 25, and 50 µmol/L) of the tested POPs, and incubated at 37 o C for 4 and 24 h, respectively. Cytotoxicity studies were performed on isolated human peripheral blood lymphocytes which were stained with acridine orange and ethidium bromide, and then viewed under a fluorescence microscope. The genotoxicity was tested in whole blood by alkaline comet assay (microgel electrophoresis). The percentage of tail DNA was used to determine the level of DNA damage. The obtained cytotoxicity results indicated that neither SnPd12 nor PbPd12 induced statistically significant alterations of cell viability related to the control, at all of the investigated concentrations. Moreover, the results of the comet assay showed that none of the tested POPs resulted in a statistically significant relative increase of tail DNA. Accordingly, both SnPd12 and PbPd12 could be considered as safe promising antileukaemic drugs from a cyto/genotoxicity point of view.