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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(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]

A new ligand TCPI and its three ruthenium(II) polypyridyl complexes [Ru(N-N) 2 (TCPI)](PF 6 ) 2 (N-N = bpy: 2,2′-bipyridine 1 ; phen: phenanthroline 2 ; dmp: 2,9-dimethyl-1,10-phenanthroline 3 ) were synthesized and characterized by elemental analysis, ESI-MS, 1 H NMR, IR, absorption and emission spectra. The cytotoxic activity in vitro of the ligand and complexes against cancer cells SGC-7901, PC-12, HepG-2, SiHa, Eca-109, HeLa and normal cell LO2 was evaluated by MTT method. Complex 3 shows the highest cytotoxic activity toward SGC-7901 cell among the complexes. Interestingly, the complexes show low or no cytotoxic activity against normal cell LO2. The apoptosis in SGC-7901 cell was investigated with AO/EB staining method. The ROS levels and the changes of mitochondrial membrane potential were studied under fluorescent microscope and flow cytometry. The cell invasion, cell cycle arrest and the expression of Bcl-2 family proteins were studied in detail. The results demonstrate that the complexes induce apoptosis in SGC-7901 cell through a ROS-mediated mitochondrial dysfunction pathway, which was accompanied by the regulation of Bcl-2 family proteins. [ABSTRACT FROM AUTHOR]

Four new ruthenium(II) polypyridyl complexes [Ru( N - N ) 2 (bddp)](ClO 4 ) 2 1–4 (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 , bddp = benzilo[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 cell lines was investigated by MTT method. The complexes show high cytotoxic activity toward the selected cell lines with an IC 50 value ranging from 5.3 ± 0.6 to 15.7 ± 3.6 μM. The apoptosis was studied with acridine orange (AO)/ethdium bromide (EB) and Hoechst 33258 staining methods. The cellular uptake was investigated with DAPI staining method. The reactive oxygen species (ROS) and mitochondrial membrane potential were performed under fluorescent microscope and flow cytometry. The complexes can induce an increase in the ROS levels and a decrease in the mitochondrial membrane potential. The comet assay was studied with fluorescent microscope. The percentage in apoptotic and necrotic cells and cell cycle arrest were assayed by flow cytometry. The effects of the complexes on the expression of caspases and Bcl-2 family proteins were studied by western blot analysis. The results show that the complexes induce apoptosis in A549 cells through an ROS-mediated mitochondrial dysfunction pathway, which was accompanied by regulating the expression of Bcl-2 family proteins. [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]

An Ir(III) organometallic complex, [Ir(ppy) 2 (paip)]PF 6 ( 1 ), (ppy and paip denote 2-phenylpyridine and 2-(4-aminophenyl) imidazo [4,5-f] [1,10] phenanthroline, respectively) was synthesized and characterized by elemental analysis, ESI-MS, 1 H and 13 C NMR. The cytotoxic activity in vitro of the complex was evaluated by MTT (MTT = (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)) method. The complex shows higher cytotoxic activity against PC-12 cells than cisplatin. The intracellular ROS generation and mitochondrial membrane potential (MMP) changes were determined by fluorescent microscope and flow cytometry. The cellular uptake and location of complex 1 , as well as cell cycle distribution and matrigel invasion in PC-12 cells treated with the complex were investigated. Meanwhile, Bcl-2 family proteins expression was also explored by western blot. The results indicate that the complex shows efficient cellular uptake and cumulates in nucleus as well as in mitochondria, and inhibits both the growth at G0/G1 phase and the invasion in extracellular matrix. It is rationally concluded that complex 1 induces apoptosis in PC-12 cell through a ROS-mediated mitochondrial dysfunction pathway with an increase in ROS level and a decrease in MMP. [ABSTRACT FROM AUTHOR]

Two new ligand PTTP (2-phenoxy-1,4,8,9-tetraazatriphenylene) and FTTP (2-(3-fluoronaphthalen-2-yloxy)-1,4,8,9-tetraazatriphenylene) and their six ruthenium(II) polypyridyl complexes [Ru(N-N) 2 (PTTP)](ClO 4 ) 2 and [Ru(N-N) 2 (FTTP)](ClO 4 ) 2 (N-N = dmb: 4,4′-dimethyl-2,2′-bipiridine; dmp: 2,9-dimethyl-1,10-phenanthroline; ttbpy: 4,4′-ditertiarybutyl-2,2′-bipyridine) were synthesized and characterized. The cytotoxic activity of the complexes against cancer cells HeLa, BEL-7402, A549, HepG-2, HOS and normal cell LO2 was evaluated by MTT method. The IC 50 values range from 1.5 ± 0.1 to 55.9 ± 7.5 μM. Complex 3 shows the highest cytotoxic activity toward BEL-7402 cells (IC 50 = 1.5 ± 0.1 μM). Complex 5 displays most effective inhibition of the cell growth in A549 and HOS cells with low IC 50 values of 2.5 ± 0.6 and 2.6 ± 0.1 μM, respectively. The apoptosis, reactive oxygen species, mitochondrial membrane potential, DNA damage, autophagy and anti-metastasis assay were investigated under a fluorescent microscope. The cell cycle arrest was assayed by flow cytometry, and the expression of caspases and Bcl-2 family proteins was studied by western blot. The results obtained show that the complexes induce apoptosis in BEL-7402 cells through a ROS-mediated mitochondrial dysfunction pathway. [ABSTRACT FROM AUTHOR]

A new ligand BTCP and its iridium(III) complex [Ir(ppy)(BTCP)]PF ( Ir-1) were synthesized and characterized by elemental analysis, ESI-MS, IR, H NMR and C NMR. The cytotoxic activity in vitro of the ligand and its complex against SGC-7901, HeLa, HOS, PC-12, BEL-7402, MG-63, SiHa, A549, HepG2 and normal cell LO2 were evaluated by MTT method [MTT = (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)]. The apoptosis was assayed with AO/EB and Hoechst 33258 staining methods. The reactive oxygen species (ROS), mitochondrial membrane potential, autophagy and cell invasion were studied under fluorescent microscope. The expression of caspases and Bcl-2 family proteins were investigated by western blot. The IC values of complex toward SGC-7901, BEL-7402 and MG-63 cells are 3.9 ± 0.5, 5.4 ± 1.2 and 4.2 ± 0.6 µM. The complex can increase the levels of ROS, and induce a decrease in the mitochondrial membrane potential. Ir-1 inhibits the cell growth at G0/G1 phase in SGC-7901 cells, and the complex can induce both autophagy and apoptosis and inhibit the cell invasion. And the complex induces 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]

A new ligand PFPIP (PFPIP = 2-(2,3,4,5,6-pentafluorophenyl)[4,5- f ]imadazo [1,10]phenanthroline) and its four ruthenium(II) polypyridyl complexes [Ru(N N) 2 (PFPIP)](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 by elemental analysis, IR, 1 H NMR, 13 C NMR and ESI-MS. The cytotoxic activity in vitro of the ligand and complexes toward BEL-7402, A549, HeLa, HepG2 and MG-63 cell lines was evaluated using MTT method (MTT = (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide). Complexes 1 , 3 and 4 show moderate cytotoxic effect on the cell growth in BEL-7402 cells with IC 50 values of 32.1 ± 0.9, 37.9 ± 1.7 and 42.1 ± 3.0 μM, respectively. The apoptosis in BEL-7402 cell was investigated with AO/EB and Hoechst 33,258 staining methods. The autophagy in BEL-7402 cell induced by complexes was assayed using MDC staining cell nuclei. The cell invasion, reactive oxygen species (ROS), mitochondrial membrane potential, cell cycle arrest, cellular uptake, comet assay and wound healing were studied under a fluorescent microscope. The complexes can cause autophagy and inhibit the cell invasion, and increase the ROS levels and induce a decrease in the mitochondrial membrane potential. The expression of the proteins related with apoptosis induced by the complexes was assayed by western blot analysis. [ABSTRACT FROM AUTHOR]

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(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 ruthenium(II) polypyridyl complex [Ru(dmp) 2 (pddppn)](ClO 4 ) 2 Ru1 was synthesized and characterized. The cytotoxic activity in vitro of the complex was evaluated by MTT method. Ru1 shows high effect on the inhibition of the cell growth against BEL-7402, HeLa, MG-63 and A549 cells with low IC 50 values of 1.6 ± 0.4, 9.0 ± 0.8, 1.5 ± 0.2 and 1.5 ± 0.3 μM, respectively. The cellular uptake indicates that Ru1 can enter into the cytoplasm and accumulate in the cell nuclei. Ru1 can induce apoptosis in A549 cells and enhance the levels of reactive oxygen species (ROS) and induce the decrease of mitochondrial membrane potential. In addition, Ru1 can down-regulate the levels of Bcl-2, Bcl-x, Bak, and Bim expression and up-regulate the expression of Bag-1 and Bad. The complex induces apoptosis of A549 cells through an intrinsic ROS-mediated mitochondrial dysfunction pathway, which was accompanied by regulating the expression of caspases and Bcl-2 family proteins. [ABSTRACT FROM AUTHOR]