Yang-Yin Xie

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.

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.

Cytotoxicity In Vitro, Apoptosis, Cellular Uptake, Cell Cycle Distribution, Mitochondrial Membrane Potential Detection, DNA Binding, and Photocleavage of Ruthenium(ii) Complexes

Four new ruthenium(ii) complexes [Ru(bpy)2(NHPIP)](ClO4)2 (Ru-1), [Ru(phen)2(NHPIP)](ClO4)2 (Ru-2), [Ru(bpy)2(AHPIP)](ClO4)2 (Ru-3), and [Ru(phen)2(AHPIP)](ClO4)2 (Ru-4) (bpy = 2,2′-bipyridine; phen = 1,10-phenanthroline; NHPIP = 2-(3-nitro-4-hydroxylphenyl)imidazo[4,5-f][1,10]phenanthroline; AHPIP = 2-(3-amino-4-hydroxylphenyl)imidazo[4,5-f][1,10]phenanthroline) were synthesized and characterized by elemental analysis, electrospray mass spectrometry, and 1H NMR spectroscopy. The cytotoxicity in vitro of these complexes against BEL-7402, HeLa, MG-63, and MCF-7 cells was evaluated by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) method. Ru-4 shows the highest cytotoxic activity towards the selected cell lines among the four complexes. The morphological apoptosis was assayed by an acridine orange/ethidium bromide staining method, and the percentages of necrotic and apoptotic cells were determined by flow cytometry. The cellular uptake and the cell cycle arrest in BEL-7402 cell was investigated. The results showed these complexes inhibit the proliferation of BEL-7402 cells at G0/G1 phase arrest. The detection of mitochondrial membrane potentials using the fluorescence probe JC-1 (5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolcarbocyanine iodide) exhibited that the mitochondrial membrane potentials decrease. Upon irradiation, these complexes can effectively cleave pBR322 DNA.

Cytotoxicity, Cell Cycle Arrest, Antioxidant Activity and Interaction of Dibenzoxanthenes Derivatives with DNA

In this study, we report the DNA interaction and cytotoxicity of four dibenzoxanthene compounds 1-4. The binding behaviors of these compounds to calf thymus DNA were studied by absorption titration, viscosity measurements. The DNA binding constants of compounds 1, 2, 3, and 4 are 5.05×10(4), 2.13×10(3), 5.10×10(4), and 3.03×10(3) M(-1), respectively. The lipophilicity of the compounds was determined by the shake flask method. The cytotoxicity of these compounds has been assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. These compounds exhibit high activity against BEL-7402, Hela, MG-63, and SKBR-3 cells. The cell cycle arrest was analyzed by flow cytometry. These compounds inhibit S phase of BEL-7402 and SKBR-3 cells. The experiments on antioxidant activity show that these compounds exhibit good antioxidant activity against hydroxyl radical ((•)OH).

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.

Synthesis, DNA-binding, photocleavage, cytotoxicity, and apoptosis studies of ruthenium(II) complexes containing 3,6-dimethyldipyrido[3,2-a:2′,3′-c]phenazine

Two new ruthenium(II) polypyridyl complexes, [Ru(bpy)2(DMDPPZ)](ClO4)2 (1) (bpy = 2,2′-bipyridine, DMDPPZ = 3,6-dimethyldipyrido[3,2-a:2′,3′-c]phenazine) and [Ru(dmb)2(DMDPPZ)](ClO4)2 (2) (dmb = 4,4′-dimethyl-2,2′-bipyridine), have been synthesized and their DNA-binding, photoinduced DNA cleavage, and cell cytotoxicity are studied. The complexes show good binding to calf thymus DNA in the order: 1 > 2. Both complexes exhibit efficient DNA cleavage upon irradiation via a mechanistic pathway involving formation of singlet oxygen as the reactive species. The cytotoxic activity of 1 and 2 was tested by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) method. These complexes effectively inhibit the proliferation of tumor cells. The antioxidant activity against hydroxyl radical (•OH) was also explored.

Synthesis, molecular structure, DNA interaction and antioxidant activity of novel naphthoxazole compound

A novel naphthoxazole compound 1 was synthesized and characterized. The crystal structure of the compound shows that N atom locates at β-position and oxygen atom at α-position in naphthalene cycle. The DNA binding was studied by absorption spectroscopy, viscosity and luminescence spectra. The DNA binding constant was determined to be 6.16×10(3). The stoichiometry of compound/DNA is 1:1. The pBR322 DNA cleavage induced by the compound was investigated. The antioxidant activity of the compound against hydroxyl radical was also explored.