A comparative study on in vitro cytotoxicity, cellular uptake, localization and apoptosis-inducing mechanism of two ruthenium(II) complexes

Autor: Yao Zhang, Guo-dong Li, Xinming Jie, Jiao-yue Qu, Xiaofeng Huang, Baojun Li, Jincan Chen, Ying Cui, Lanmei Chen, Zhilin Zou
Rok vydání: 2018
Předmět:
Zdroj: Transition Metal Chemistry. 43:149-159
ISSN: 1572-901X
0340-4285
Popis: Two ruthenium complexes [Ru(MeIm)4(bpy)]2+ (Ru1, MeIm = 1-methylimidazole, bpy = 2,2′-bipyridine) and [Ru(Im)4(bpy)]2+ (Ru2, Im = imidazole) with the same PF 6 − counter-ion but different lipophilicities were synthesized and characterized and as potent anticancer agents. The relationships between cellular uptake, localization and molecular action mechanisms of these complexes were elucidated. The results showed that Ru1 with higher logPo/w exhibited faster cellular uptake rates, but lower anticancer activity than Ru2. In addition, Ru1 predominantly accumulated in the mitochondria and cytoplasm, and induced G0/G1 cell cycle arrest, whereas the more hydrophilic Ru2 tended to localize and accumulate in the cell nucleus and mitochondria. Further mechanism studies indicated that Ru2 caused cell cycle arrest at S phase by regulating cell cycle related proteins and induced apoptosis in A549 cells through DNA damage, cellular ROS accumulation, activation of the caspase pathway and mitochondrial dysfunction.
Databáze: OpenAIRE
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