In vitro evaluation of the enantiomeric R- and S-1,1'-binaphthyl-2,2'-diaminodichlorido-Pt(ii) complexes in human Burkitt lymphoma cells: emphasis on cellular accumulation, cytotoxicity, DNA binding, and ability to induce apoptosis.

The aim of this project is to gain insights into the uptake and cellular actions of the enantiomeric R- and S-1,1'-binaphthyl-2,2'-diaminodichlorido-Pt(ii) complexes (R- and S-[Pt(DABN)Cl]) in the cisplatin-sensitive human Burkitt lymphoma cell line (Gumbus, IC: 1.3 ± 0.2 μM) and its cisplatin-resistant sub-line (CDDPrGB, IC: 6.6 ± 1.2 μM). The cellular uptakes of R- and S-[Pt(DABN)Cl] are ca. 4-fold higher than cisplatin, and involve a transport mechanism independent of the volume-sensitive, organic anion-channel complex, which facilitates cisplatin accumulation. The cisplatin-resistant CDDPrGB cells are not cross-resistant to either S- or R-[Pt(DABN)Cl]. We also find that even though R-[Pt(DABN)Cl] has a higher maximal cellular uptake and binds at higher levels to calf-thymus DNA than S-[Pt(DABN)Cl], it appears that S-[Pt(DABN)Cl] is more cytotoxic for Gumbus (IC: 0.4 ± 0.1 μM) compared to R-[Pt(DABN)Cl] (IC: 0.7 ± 0.3 μM). The cellular action of R- and S-[Pt(DABN)Cl] involves G0/G1 cell cycle arrest and cell death involving the extrinsic and intrinsic apoptotic pathways.