Guang-Bin Jiang

The induction of apoptosis in BEL-7402 cells through the ROS-mediated mitochondrial pathway by a ruthenium(II) polypyridyl complex

A new Ru(II) polypyridyl complex [Ru(phen)2(addppn)](ClO4)2 (Ru1) has been synthesized and characterized. The DNA-binding constant of the complex with DNA was determined to be 1.93 (±0.12) × 106 M−1. The complex interacts with DNA by an intercalative mode. Cytotoxicity in vitro, apoptosis, cell cycle distribution, apoptotic pathway, reactive oxygen species and mitochondrial membrane potential assays were performed. The IC50 values of Ru1 toward BEL-7402, HeLa, MG-63 and SKBR-3 cell lines are 3.9 ± 0.4, 9.0 ± 0.8, 6.6 ± 0.6 and 5.1 ± 0.6 μM, respectively. Interestingly, Ru1 shows a higher cytotoxicity than cisplatin on BEL-7402 cells under identical conditions. Ru1 can effectively induce apoptosis in BEL-7402 and induces cell cycle arrest at the G0/G1 phase in BEL-7402 cells and at the G2/M phase in SKBR-3 cells. In addition, Ru1 can enhance the level of reactive oxygen species and induce the decrease of the mitochondrial membrane potential. Western blot analysis shows that Ru1 activates caspase-3 and -7, down-regulates the expression of the anti-apoptotic proteins of Bcl-x and Bag-1, and upregulates the levels of the proapoptotic proteins of Bad, Bak, Bax and Bim in BEL-7402 cells. These results show that Ru1 induces apoptosis in BEL-7402 cells through an ROS-mediated mitochondrial dysfunction pathway.

Synthesis, characterization, DNA interaction, antioxidant and anticancer activity studies of ruthenium(II) polypyridyl complexes.

Two new Ru(II) polypyridyl complexes [Ru(phen)₂(adppz)](ClO₄)₂ (1) and [Ru(dip)₂(adppz)](ClO₄)₂ (2) have been synthesized and characterized. The DNA-binding constants were determined to be 6.54 ± 0.42 × 10(5) and 7.65 ± 0.20 × 10(5)M(-1) for complexes 1 and 2. DNA binding experiments indicated that complexes 1 and 2 interact with DNA through intercalative mode. Antioxidant activity shows that the complexes have significant hydroxyl radical scavenging activity. Cytotoxic activities suggest that the complex 2 exhibits higher cytotoxic activity against BEL-7402, MG-63 and SKBR-3 cells than complex 1 under identical conditions. Complexes 1 and 2 can induce apoptosis of BEl-7402 cells. We have identified several cellular mechanisms induced by 1 and 2 in BEL-7402 cells, including the level detection of ROS, activation of procaspase 3, caspase 7, the expression of antiapoptotic proteins Bcl-x, Bcl-2, proapoptotic proteins Bad, Bax, Bid and cell cycle arrest. Thus, complexes 1 and 2 inhibit growth of BEL-7402 cells through induction of apoptotic cell death, enhancement of ROS levels and S-phase and G0/G1 cell cycle arrest. Further investigations have shown that complex 2 induces apoptosis by regulating the expression of Bcl-2 family proteins.

Ruthenium(II) complexes: DNA-binding, cytotoxicity, apoptosis, cellular localization, cell cycle arrest, reactive oxygen species, mitochondrial membrane potential and western blot analysis.

The aim of our study was to investigate DNA-binding and cytotoxic activity of the four new Ru(II) polypyridyl complexes [Ru(dmb)₂(HMHPIP)](ClO₄)₂ (1), [Ru(bpy)₂(HMHPIP)](ClO₄)₂ (2), [Ru(phen)₂(HMHPIP)](ClO₄)₂ (3) and [Ru(dmp)₂(HMHPIP)](ClO₄)₂ (4). The complexes interact with DNA through intercalative mode and show relatively high cytotoxic activity against A549 cells, no cytotoxicity toward MG-63 cells. Complexes 1-4 can enhance the levels of ROS in A549 cells and induce the decrease of the mitochondrial membrane potential. These complexes inhibit the cell growth in A549 cells at G0/G1 or S phase. Complex 3 activated caspase 7, and down-regulated the expression of the anti-apoptotic protein Bcl-2. Complexes 1-4 induce apoptosis in A549 cells through ROS-mediated mitochondrial dysfunction pathway.

Cytotoxic activity, DNA damage, cellular uptake, apoptosis and western blot analysis of ruthenium(II) polypyridyl complex against human lung decarcinoma A549 cell

A new ruthenium(II) polypyridyl complex [Ru(dmp)2(pddppn)](ClO4)2Ru1 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 IC50 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.

Cytotoxicity in vitro, cell migration and apoptotic mechanism studies induced by ruthenium(II) complexes

Four new ruthenium(II) polypyridyl complexes [Ru(dmb)2(DHBT)](ClO4)2 (1) (DHBT = 12,14-dihydroxyl-4,5,9,10,11,13-hexaazabenzo[b]triphenylene, dmb = 4,4′-dimethyl-2,2′-bipyridine), [Ru(bpy)2(DHBT)](ClO4)2 (2) (bpy = 2,2′-bipyridine), [Ru(phen)2(DHBT)](ClO4)2 (3) (phen = 1,10-phenanthroline) and [Ru(dmp)2(DHBT)](ClO4)2 (4) (dmp = 2,9-dimethyl-1,10-phenanthroline) were synthesized and characterized. The cytotoxicity in vitro of these complexes was evaluated against human HepG-2, HeLa, A549, MG-63 and BEL-7402 cancer cell lines. The IC50 values of the complexes toward selected cell lines range from 14.9 ± 1.1 to 30.1 ± 2.7 μM. The cytotoxicity and the levels of reactive oxygen species were found to increase with increasing concentrations of the complexes. The complexes are sensitive to MG-63 cells and can inhibit the MG-63 cell migration. Morphological and comet assay studies show that the complexes can effectively induce apoptosis in MG-63 cells. Complex 2 inhibits the cell growth at the G0/G1 phase, whereas the other complexes exhibit the antiproliferative mechanism at the S phase in the MG-63 cell line. The complexes can downregulate the expression of Bcl-2 protein and upregulate the levels of Bad protein in MG-63 cells. The complexes induce MG-63 cells apoptosis through a ROS-mediated mitochondrial dysfunction pathway.

Synthesis, characterization, in vitro cytotoxicity, and apoptosis-inducing properties of ruthenium(II) complexes.

Two new Ru(II) complexes, [Ru(bpy)2(FAMP)](ClO4)2 1 and 2, are synthesized and characterized by elemental analysis, electrospray mass spectrometry, and 1H nuclear magnetic resonance. The in vitro cytotoxicities and apoptosis-inducing properties of these complexes are extensively studied. Complexes 1 and 2 exhibit potent antiproliferative activities against a panel of human cancer cell lines. The cell cycle analysis shows that complexes 1 and 2 exhibit effective cell growth inhibition by triggering G0/G1 phase arrest and inducing apoptosis by mitochondrial dysfunction. The in vitro DNA binding properties of the two complexes are investigated by different spectrophotometric methods and viscosity measurements.

The studies on bioactivity in vitro of ruthenium(II) polypyridyl complexes towards human lung carcinoma A549 cells

Three Ru(II) polypyridyl complexes [Ru(dmb)2(HDPIP)](ClO4)2 (1), [Ru(bpy)2(HDPIP)](ClO4)2 (2) and [Ru(phen)2(HDPIP)](ClO4)2 (3) were synthesized and characterized. The IC50 values of the complexes against BEL-7402, A549, MG-63 and SK-BR-3 cells range from 20.8 ± 1.6 to 7.3 ± 1.0 μM. Complexes 1, 2 and 3 can enhance the ROS levels and enter into the cytoplasm and accumulate in the cell nuclei. All the complexes can induce a decrease of the mitochondrial membrane potential and inhibit the cell growth in A549 cells in the G0/G1 phase. Complex 3 has no obvious impact on the expression of the anti-apoptotic protein Bcl-2, and increases the levels of the pro-apoptotic proteins Bax and Bid. Complex 3 induces apoptosis of A549 cells through a ROS-mediated mitochondrial dysfunction pathway.

DNA interaction, antioxidant activity, and bioactivity studies of two ruthenium(II) complexes

Two new ruthenium(II) polypyridyl complexes [Ru(dmb)2(dcdppz)](ClO4)2 (1) and [Ru(bpy)2(dcdppz)](ClO4)2 (2) were prepared and characterized. The crystal structure of the complex 2 was solved by single crystal X-ray diffraction. The complex crystallizes in the monoclinic system, space group P21/n with a=12.9622(14)Å, b=17.1619(19)Å, c=22.7210(3)Å, β=100.930(2)(°), R=0.0536, Rω=0.1111. The DNA-binding constants for complexes 1 and 2 were determined to be 1.92×10(5) (s=1.72) and 2.24×10(5) (s=1.86)M(-1), respectively. The DNA-binding behaviors showed that complexes 1 and 2 interact with DNA by intercalative mode. The antioxidant activities of the ligand and the complexes were performed. Ligand, dcdppz, has no cytotoxicity against the selected cell lines. Complex 1 shows higher cytotoxicity than complex 2, but lower than cisplatin toward selected cell lines. The apoptosis and cell cycle arrest were investigated, and the apoptotic mechanism of BEL-7402 cells was studied by reactive oxygen species (ROS), mitochondrial membrane potential and western blot analysis. Complex 1 induces apoptosis in BEL-7402 cells through ROS-mediated mitochondrial dysfunction pathway and by regulating the expression of Bcl-2 family proteins.

Cytotoxicity, cellular uptake, cell cycle arrest, apoptosis, reactive oxygen species and DNA-binding studies of ruthenium(II) complexes

Three ruthenium(II) polypyridyl complexes [Ru(dmb)2(dadppz)]2+1, [Ru(bpy)2(dadppz)]2+2 and [Ru(phen)2(dadppz)]2+3 were synthesized and characterized by elemental analysis, ES-MS, 1H NMR and 13C NMR. Their DNA-binding behaviors were investigated by absorption titration, fluorescence spectroscopy and viscosity measurements. Cytotoxicity in vitro, apoptosis, cell cycle arrest, cellular uptake and reactive oxygen species assays were performed. The complexes were found to show moderate DNA-binding affinities and high cytotoxicities toward A549, BEL-7402, MG-63 and SKBR-3 cell lines. These complexes can effectively induce apoptosis of BEL-7402. In cell cycle assays, the complexes induced S-phase arrest on BEL-7402 cells and G0/G1-phase arrest on SKBR-3 cells. The DNA-binding experiments showed that the three complexes interact with CT-DNA through an intercalative mode.

DNA-binding, antioxidant activity, and bioactivity studies of ruthenium(II) complexes containing amino substituents

Two new Ru(II) complexes, [Ru(dmp)2(dadppz)](ClO4)2 (1) and [Ru(dip)2(dadppz)](ClO4)2 (2), were synthesized and characterized by elemental analysis, ES-MS, and 1H NMR. DNA-binding behaviors were investigated by absorption titration and luminescence spectra. The DNA-binding constants were 3.1 (± 0.2) × 104 and 3.0 (± 0.2) × 105 M−1 for 1 and 2. The antioxidant activity of these complexes against hydroxyl radical ( ) was explored. The cytotoxicities in vitro towards A549, BEL-7402, MG-63, and SKBR-3 cells were studied by 3-(4,5dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. Complex 1 shows high cytotoxicity, but 2 is not cytotoxic towards the selected cell lines. Apoptosis and cell cycle distribution were studied by flow cytometry. The cellular uptake showed that complexes can enter into the cytoplasm. JC-1 was used as a fluorescence probe in detecting the mitochondrial membrane potential and results indicate that the mitochondrial membrane potential decreases.