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Issue 2, 2018
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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

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Abstract

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)Cl2]) in the cisplatin-sensitive human Burkitt lymphoma cell line (Gumbus, IC50: 1.3 ± 0.2 μM) and its cisplatin-resistant sub-line (CDDPrGB, IC50: 6.6 ± 1.2 μM). The cellular uptakes of R- and S-[Pt(DABN)Cl2] 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)Cl2]. We also find that even though R-[Pt(DABN)Cl2] has a higher maximal cellular uptake and binds at higher levels to calf-thymus DNA than S-[Pt(DABN)Cl2], it appears that S-[Pt(DABN)Cl2] is more cytotoxic for Gumbus (IC50: 0.4 ± 0.1 μM) compared to R-[Pt(DABN)Cl2] (IC50: 0.7 ± 0.3 μM). The cellular action of R- and S-[Pt(DABN)Cl2] involves G0/G1 cell cycle arrest and cell death involving the extrinsic and intrinsic apoptotic pathways.

Graphical abstract: 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

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Publication details

The article was received on 14 Aug 2017, accepted on 18 Dec 2017 and first published on 18 Dec 2017


Article type: Paper
DOI: 10.1039/C7MT00237H
Citation: Metallomics, 2018,10, 323-336
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    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

    B. H. Sørensen, P. Werth, I. H. Lambert and P. J. Bednarski, Metallomics, 2018, 10, 323
    DOI: 10.1039/C7MT00237H

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