Abstract
Two ruthenium(II) polypyridyl complexes formulated as [Ru(bpy)2(THPDP)](PF6)2 (1) and [Ru(ttbpy)2(THPDP)](PF6)2 (ttbpy = 4,4ʹ-ditertiary butyl-2,2ʹ-bipyridine) (2) were synthesized and characterized by elemental analysis, 1H NMR, 13C NMR and UV–Vis spectra. The cytotoxic activities of the complexes against cancer cell lines BEL-7402, A549, SGC-7901, HeLa and normal NIH3T3 cells were investigated by 3-(4,5-dimethylthiazole)-2,5-diphenyltetrazolium bromide (MTT) methods. The complexes show moderate cytotoxicity toward BEL-7402 and HeLa cells. The changes in mitochondrial membrane potential, intracellular Ca2+ and reactive oxygen species were studied by fluorescence microscopy. Both complexes can increase intracellular Ca2+ concentrations and ROS levels and induce a decrease in mitochondrial membrane potential. They also inhibit cell invasion and suppress cell proliferation at the G0/G1 phase. Additionally, they activate caspase 3, cleave PARP and regulate the expression of Bcl-2 family proteins. In short, the complexes induce apoptosis in BEL-7402 cells through a ROS-mediated mitochondria dysfunction pathway.
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Acknowledgements
We are grateful to Science and Technology Project of Jiangxi Education Department in 2017 (No GJJ171024) and Jiangxi University of Technology for financial support.
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Liang, ZH., Wang, YN., Xiong, ZW. et al. Studies of the anticancer activities of ruthenium(II) polypyridyl complexes toward human hepatocellular carcinoma BEL-7402 cells. Transit Met Chem 44, 585–594 (2019). https://doi.org/10.1007/s11243-019-00315-5
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DOI: https://doi.org/10.1007/s11243-019-00315-5