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.

中文翻译：

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对人类Burkitt淋巴瘤细胞中对映体R-和S -1,1'-联萘-2,2'-二氨基二氯-Pt（ii）复合物的体外评估：强调细胞蓄积，细胞毒性，DNA结合和诱导能力凋亡

该项目的目的是深入了解对映体R-和S -1,1'-联萘-2,2'-二氨基二氯-Pt（II）配合物（R-和S- [Pt （DABN）Cl ₂ ]）在顺铂敏感的人类Burkitt淋巴瘤细胞系（Gumbus，IC ₅₀：1.3±0.2μM）和其对顺铂耐药的亚系（CDDPrGB，IC ₅₀：6.6± 1.2μM ）中。R-和S- [Pt（DABN）Cl ₂ ]的细胞摄取约为。比顺铂高4倍，并且涉及一种与体积敏感的有机阴离子通道络合物无关的转运机制，从而促进了顺铂的积累。顺铂耐药的CDDPrGB细胞对S-或R- [Pt（DABN）Cl ₂ ]均无交叉耐药性。我们还发现，尽管与S- [Pt（DABN）Cl ₂ ]相比，R- [Pt（DABN）Cl ₂ ]具有更高的最大细胞摄取并以更高的水平与小牛胸腺DNA结合，但似乎S- [的Pt（DABN）氯₂ ]是用于Gumbus（IC多种细胞毒性₅₀相比：0.4±0.1μM）- [R [PT（DABN）Cl -的₂ ]（IC₅₀：0.7±0.3μM）。R-和S- [Pt（DABN）Cl ₂ ]的细胞作用涉及G0 / G1细胞周期停滞和细胞死亡，涉及外在和内在的凋亡途径。