Protein binding and anticancer activity studies of ruthenium(II) polypyridyl complexes toward BEL-7402 cells

• Published in: Journal of photochemistry and photobiology. B, Biology Biology, 2016-05, Vol.158, p.39-48
• Main Authors: Lai, Shang-Hai, Li, Wei, Yao, Jun-Hua, Han, Bing-Jie, Jiang, Guang-Bin, Zhang, Cheng, Zeng, Chuan-Chuan, Liu, Yun-Jun
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Apoptosis - drug effects; Caspases - metabolism; Cell Cycle - drug effects; Cell Line, Tumor; Cytotoxicity in vitro; DNA Damage; Humans; Membrane Potential, Mitochondrial - drug effects; Mitochondrial membrane potential; Protein Binding; Proto-Oncogene Proteins c-bcl-2 - metabolism; Pyridines - chemistry; Reactive oxygen species; Reactive Oxygen Species - metabolism; Ru (II) polypyridyl complexes; Ruthenium Compounds - chemistry; Ruthenium Compounds - pharmacology; Spectrum Analysis - methods; Western blot analysis
• ISSN: 1011-1344; 1873-2682
• DOI: 10.1016/j.jphotobiol.2016.02.015

Four new ruthenium(II) polypyridyl complexes [Ru(dmb)2(dqtbt)](ClO4)2 (1) (dqtbt=12-(2,3-diphenyl-quinoxalin-6-yl)-4,5,10,13-tetraazabenzo[b]triphenylene, dmb=4,4′-dimethyl-2,2′-bipyridine), [Ru(bpy)2(dqtbt)](ClO4)2 (2) (bpy=2,2′-bipyridine), [Ru(phen)2(dqtbt)](ClO4)2 (3) (phen=1,10-phenanthroline) and [Ru(dmp)2(dqtbt)](ClO4)2 (4) (dmp=2,9-dimethyl-1,10-phenanthroline) were synthesized and characterized. The cytotoxicity in vitro of the complexes was evaluated against human BEL-7402, A549, HeLa, HepG-2 and MG-63 cancer cell lines. These complexes are sensitive to BEL-7402 cells, the IC50 values are 4.9±0.5, 4.6±0.4, 7.7±1.8 and 1.9±0.3μM toward BEL-7402 cells. The complexes can increase the levels of reactive oxygen species and induce the decrease of mitochondrial membrane potential. Morphological and comet assay studies show that the complexes can effectively induce apoptosis in BEL-7402 cells. Complexes 1–4 inhibit the cell growth at G0/G1 phase in BEL-7402 cell line. The complexes can downregulate the expression of Bcl-2 and Bcl-x proteins and upregulate the levels of Bid protein in BEL-7402 cells. The results show that the complexes induce BEL-7402 cell apoptosis through a ROS-mediated mitochondrial dysfunction pathway. In addition, the complexes show strong protein-binding affinities. Four new Ru(II) complexes were synthesized and characterized. The cytotoxicity in vitro, apoptosis, comet assay, ROS, mitochondrial membrane potential, cell cycle arrest, expression of proteins and protein-binding were investigated. [Display omitted] •Four new ruthenium(II) complexes were synthesized and characterized.•Cytotoxicity of complexes toward HepG-2, HeLa, MG-63, A549, BEL-7402 was studied.•The apoptosis, comet assay, cellular uptake, ROS, cell cycle arrest were studied.•The expression of Bcl-2 family proteins was assayed by western blot analysis.•The protein-binding of the complexes with BSA was investigated.