A large number of
cancers are treated with
cisplatin (CDDP). However, its use is limited by drug resistance, which is often related to intracellular levels of
thiol-containing molecules such as
glutathione (GSH). The role of GSH in
cisplatin-resistant
cancer cells is still unclear. GSH may form adducts with CDDP which results in the deactivation of the
drug, and, actually, a high intracellular level of GSH was observed in some
cisplatin-resistant
cancers. To overcome drug resistance, CDDP is often administered in combination with one or more drugs to exploit a possible synergistic effect. In previous studies, we observed that the sensitivity to CDDP of leukemic and ovarian
cisplatin-resistant
cancer cells was restored in the presence of [
Cu(phen)2(H2O)](ClO4)2 (C0) (phen is 1,10-phenathroline). In order to clarify the possible interactions between GSH and CDDP, the reactivity and competitive reactions among CDDP, C0 and GSH in binary and ternary mixtures were studied. The investigation was extended also to [Cu(phen)(H2O)2(ClO4)2] (C10) and
GSSG, the oxidized form of GSH. It was observed that CDDP was able to react with the studied
copper complexes and with GSH or
GSSG. However, in mixtures containing CDDP, GSH or
GSSG and C0 or C10, only
copper-
glutathione complexes were detected, while no
platinum-
glutathione adducts were found.