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As one of the major cell regulated center, mitochondria are closely associated with cell proliferation, apoptosis of tumor cell. In this work, four new ruthenium (II) polypyridyl complexes [Ru(bpy) 2 (FTTP)](ClO 4 ) 2 ( 1 ) (FTTP = 11-(3-fluoro-naphthalen-2-yloxy)-4,5,9,14-tetraaza-benzo[ b ]triphenylene, bpy = 2,2′-bipyridine), [Ru(phen) 2 (FTTP)](ClO 4 ) 2 ( 2 ) (phen = 1,10-phenanthroline), [Ru(bpy) 2 (PTTP)](ClO 4 ) 2 ( 3 ) (PTTP = 2-phenoxy-1,4,8,9-tetraazatriphenylene) and [Ru(phen) 2 (PTTP)](ClO 4 ) 2 ( 4 ) were synthesized and characterized by elemental analysis, ESI-MS, 1 H NMR and 13 C NMR. The cytotoxic activity, ability of inhibiting cell invasion, cell cycle arrest and apoptosis-inducing mechanism of these Ru(II) complexes have been investigated in detail by MTT (3-(4,5-dimethylthiazole)-2,5-diphenyltetrazolium bromide) method, invasion assay, comet assay as well as western blotting techniques. Notably, complexes 1 – 4 displayed high cytotoxic activity against liver carcinoma HepG2 cells and the IC 50 values of complexes 1 – 4 against HepG2 cells are 10.4 ± 1.2, 9.3 ± 0.6, 29.1 ± 1.5 and 5.6 ± 1.2 μM, respectively. The comet assay showed that the complexes can induce DNA damage. The acridine orange (AO) and ethidium bromide (EB) staining method indicated that the complexes can cause apoptosis in HepG2 cells. Further studies showed that complexes 1 – 4 caused cell cycle arrest at G0/G1 phase and induced HepG2 cells apoptosis through a ROS-mediated mitochondrial dysfunction pathway, which involved an increase in the levels of reactive oxygen species (ROS), a decrease in the mitochondrial membrane potential, activation of caspases and Bcl-2 family proteins. [ABSTRACT FROM AUTHOR]

Four new ruthenium(II) polypyridyl complexes [Ru(N–N) 2 (dhbn)](ClO 4 ) 2 (N–N = dmb: 4,4′-dimethyl-2,2′-bipyridine 1 ; bpy = 2,2′-bipyridine 2 ; phen = 1,10-phenanthroline 3 ; dmp = 2,9-dimethyl-1,10-phenanthroline 4 ) were synthesized and characterized. The cytotoxicity in vitro of the ligand and complexes toward HepG-2, HeLa, MG-63 and A549 were assayed by MTT method. The IC 50 values of the complexes against the above cells range from 17.7 ± 1.1 to 45.1 ± 2.8 μM. The cytotoxic activity of the complexes against HepG-2 cells follows the order of 4 > 2 > 3 > 1 . Ligand shows no cytotoxic activity against the selected cell lines. Cellular uptake, apoptosis, comet assay, reactive oxygen species, mitochondrial membrane potential, cell cycle arrest, and the expression of proteins involved in apoptosis pathway induced by the complexes were investigated. The results indicate that complexes 1–4 induce apoptosis in HepG-2 cells through an intrinsic ROS-mediated mitochondrial dysfunction pathway. [ABSTRACT FROM AUTHOR]

Four new ruthenium(II) polypyridyl complexes [Ru(dmb) 2 (dqtbt)](ClO 4 ) 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)](ClO 4 ) 2 ( 2 ) (bpy = 2,2′-bipyridine), [Ru(phen) 2 (dqtbt)](ClO 4 ) 2 ( 3 ) (phen = 1,10-phenanthroline) and [Ru(dmp) 2 (dqtbt)](ClO 4 ) 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 IC 50 values are 4.9 ± 0.5, 4.6 ± 0.4, 7.7 ± 1.8 and 1.9 ± 0.3 μM 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. [ABSTRACT FROM AUTHOR]

A new ligand Adbdp and its four ruthenium(II) polypyridyl complexes [Ru(N-N) 2 (Adbdp)](ClO 4 ) 2 [N-N = dmb: 4,4′-dimethyl-2,2′-bipyridine 1 , bpy: 2,2′-bipyridine 2 , phen: 1,10-phenanthroline 3 and dmp: 2,9-dimethyl-1,10-phenanthroline 4 , Adbdp = acenaphtheno[2,3-b]-1,4-diazabenzo[i]dipyrido[3,2- a :2′,3′- c ]phenazine] were synthesized and characterized by elemental analysis, ESI-MS and 1 H NMR. The cytotoxicity in vitro of the complexes against BEL-7402, HeLa, MG-63 and A549 cells was studied by MTT method. The IC 50 values are 24.2 ± 1.9, 11.5 ± 3.6, 3.4 ± 0.3 and 9.7 ± 0.5 μM for complexes 1 , 2 , 3 and 4 toward A549 cells, respectively. The apoptosis was assayed with AO/EB and Hoechst 33258 staining methods. The cellular uptake was investigated with DAPI-stained cell nuclei. The reactive oxygen species and mitochondrial membrane potential were performed under fluorescent microscope. The cell cycle distribution was studied by flow cytometry and the protein expression of Bcl-2 family proteins was analyzed by western blot. The results show that the complexes induce A549 cell apoptosis through a ROS-mediated mitochondrial dysfunction pathway. [ABSTRACT FROM AUTHOR]

In this article, the in vitro cytotoxicity of platycodin D was evaluated in human PC-12, SGC-7901, BEL-7402, HeLa and A549 cancer cell lines. PC-12 cells were sensitive to platycodin D treatment, with an IC 50 value of 13.5 ± 1.2 μM. Morphological and comet assays showed that platycodin D effectively induced apoptosis in PC-12 cells. Platycodin D increased the levels of reactive oxygen species (ROS) and induced a decrease in mitochondrial membrane potential. Platycodin D induced cell cycle arrest at the G0/G1 phase in the PC-12 cell line. Platycodin D can induce autophagy. In addition, platycodin D can down-regulate the expression of Bcl-2 and Bcl-x, and up-regulate the levels of Bid protein in the PC-12 cells. The results demonstrated that platycodin D induced PC-12 cell apoptosis through a ROS-mediated mitochondrial dysfunction pathway. [ABSTRACT FROM AUTHOR]

Four new ruthenium(II) polypyridyl complexes [Ru(dmb) 2 (DQTT)](ClO 4 ) 2 ( 1 ) (DQTT = 12-(1,4-dihydroquinoxalin-6-yl)-4,5,9,14-tetraazabenzo[b]triphenylene, dmb = 4,4′-dimethyl-2,2′-bipyridine), [Ru(bpy) 2 (DQTT)](ClO 4 ) 2 ( 2 ) (bpy = 2,2′-bipyridine), [Ru(phen) 2 (DQTT)](ClO 4 ) 2 ( 3 ) (phen = 1,10-phenanthroline) and [Ru(dmp) 2 (DQTT)](ClO 4 ) 2 ( 4 ) (dmp = 2,9-dimethyl-1,10-phenanthroline) were synthesized and characterized by elemental analysis, ESI-MS, 1 H NMR and 13 C NMR. The cytotoxic activity in vitro of the complexes was evaluated against human BEL-7402, A549, HeLa, HepG-2 and MG-63 cancer cell lines by MTT (3-(4,5-dimethylthiazole)-2,5-diphenyltetrazolium bromide) method. The IC 50 values of complexes 1 – 4 against BEL-7402 cells are 31.8 ± 1.0, 35.8 ± 1.6, 29.0 ± 0.8 and 25.0 ± 0.9 μM, respectively. The morphological apoptosis was investigated with AO/EB (acridine orange/ethidium bromide) and Hoechst 33258 staining methods. The DNA damage was assayed by comet assay. The inhibition of cell migration was evaluated by the wound healing assay. The levels of ROS (reactive oxygen species) and the changes of mitochondrial membrane potential were studied under fluorescent microscope. The percentages in the cells of apoptotic and necrotic cells and the cell cycle arrest were determined by flow cytometry. The expression of Bcl-2 family proteins was investigated by western blot analysis. The results show that the complexes induce BEL-7402 cells apoptosis through a ROS-mediated mitochondrial dysfunction pathway, which was accompanied by regulation of the expression of Bcl-2 family proteins. [ABSTRACT FROM AUTHOR]