The new
platinum(IV) complex cis,trans,cis-[PtCl(2)(CH(3)
COO)(2)-(NH(3))(1-
adamantylamine)] [
adamplatin(IV)] seems promising for the perspective application in
therapy of corresponding
tumors. It is therefore of great interest to understand details of mechanisms underlying its biological efficacy. Cellular uptake of the drug, alterations in the target
DNA induced by
platinum drugs along with processing of
platinum-induced damage to
DNA and drug inactivation by
sulfur-containing compounds belong to major pharmacological factors affecting antitumor effects of
platinum compounds. We examined in the present work the significance of these factors in the mechanism of antitumor effects of
adamplatin(IV) and compared the results with those of the parallel studies performed with "conventional"
cisplatin. The results show that deactivation of
adamplatin(IV) by
sulfur-containing compounds (such as
glutathione or
metallothioneins) is likely to play a less significant role in the mechanism of resistance of
tumor cells to
adamplatin(IV) in contrast to the role of these reactions in the effects of
cisplatin. Moreover, the treatment of
tumor cells with
adamplatin(IV) does not result in
DNA modifications that would be markedly different from those produced by
cisplatin. In contrast, the effects of other factors, such as enhanced accumulation of the drug in cells, strong inhibition of
DNA polymerization by these adducts, lowered DNA repair, and
DNA-
protein cross-linking are different from the effects of these factors in the mechanism underlying activity of
cisplatin. Hence, the differences between effects of
adamplatin(IV) and
cisplatin observed in the present work on molecular level may help understand the unique activity of
adamplatin(IV).