化学
顺铂
细胞毒性
作用机理
细胞骨架
奥沙利铂
细胞生物学
DNA损伤
细胞毒性T细胞
表观遗传学
配体(生物化学)
癌细胞
立体化学
细胞
生物化学
体外
癌症研究
癌症
DNA
生物
化疗
受体
遗传学
基因
结直肠癌
作者
Hana Kostrhunová,Juraj Zajac,Vojtěch Novohradský,Jana Kašpárkova,Jaroslav Malina,Janice R. Aldrich‐Wright,Emanuele Petruzzella,Roman Sirota,Dan Gibson,Viktor Brabec
标识
DOI:10.1021/acs.jmedchem.9b00489
摘要
The substitution inert platinum agent [Pt(1S,2S-diaminocyclohexane)(5,6-dimethyl-1,10-phenanthroline)]2+ (56MeSS, 5) is a potent cytotoxic metallodrug. In contrast to conventional cisplatin or oxaliplatin, the mechanism of action (MoA) of 5 is fundamentally different. However, details of the mechanism by which the 5,6-dimethyl-1,10-phenanthroline ligand contributes to the cytotoxicity of 5 and its derivatives have not been sufficiently clarified so far. Here, we show that 5 and its Pt(IV) derivatives exhibit an intriguing potency in the triple-negative breast cancer cells MDA-MB-231. Moreover, we show that the Pt(IV) derivatives of 5 act by multimodal MoA resulting in the global biological effects, that is, they damage nuclear DNA, reduce the mitochondrial membrane potential, induce the epigenetic processes, and last but not least, the data provide evidence that changes in the organization of cytoskeleton networks are functionally important for 5 and its derivatives, in contrast to clinically used platinum cytostatics, to kill cancer cells.
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