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Two new Ru(II) polypyridyl complexes were synthesized and characterization. DNA-binding behaviors of the complexes were investigated. Most importantly, the further anticancer mechanism of the Ru(II) complexes was explored by apoptosis, cell invasion, intracellular reactive oxygen species (ROS) levels and mitochondrial membrane potentials. Two novel ruthenium(II) polypyridyl complexes [Ru(bpy) 2 (ETPIP)](ClO 4) 2 (Ru(II)-1) and [Ru(phen) 2 (ETPIP)](ClO 4) 2 (Ru(II)-2) (bpy = 2,2 ′ -bipyridine, ETPIP = 2-(4-(thiophen-2-ylethynyl)phenyl)-1 H -imidazo[4,5- f ][1,10]phenanthroline, phen = 1,10-phenanthroline) have been synthesized and characterized. The DNA binding behaviors were evaluated using electronic absorption titration, luminescence spectra and viscosity measurement, revealing an intercalative mode. The cytotoxicity of the ligand and Ru(II) complexes toward A549, HepG-2, SGC-7901 and Hela was assayed by MTT ((3-(4,5-dimethylthiazo-2-yl)-2,5-diphenyltetrazolium bromide)) method. Notably, ETPIP shows no anticancer activity against selected cell lines, and complexes Ru(II)-1 (IC 50 = 18.4 ± 2.1 μM) and Ru(II)-2 (IC 50 = 16.5 ± 1.7 μM) were found to be slightly more effective against HepG-2 cells than cisplatin (IC 50 = 26.4 ± 2.6 μM). Evaluation of cell invasion was performed with the Boyden chamber invasion assay. Additionally, the cell cycle distribution of HepG-2 cells was carried out by flow cytometry. Most importantly, the further anticancer mechanism of the Ru(II) complexes was explored by apoptosis, intracellular reactive oxygen species (ROS) levels and mitochondrial membrane potentials. These results reveal that complexes Ru(II)-1 and Ru(II)-2 could induce apoptosis in HepG-2 cells via a ROS-mediated mitochondrial dysfunction pathway. [ABSTRACT FROM AUTHOR]

Engineered silica nanoparticles (SiNP) are emerging materials for medical applications. Evaluating biological responses of specific cells treated with engineered silica nanoparticles is however essential. We synthesized and characterized the physicochemical properties of silica nanoparticles with two different sizes of 10 and 100 nm (10SiNP and 100SiNP) dispersed in cell culture medium. HuH-7, an epithelial-like human hepatoblastoma cell line and SK-HEP-1, a liver sinusoidal endothelial cell line (LSEC) are employed to evaluate their biological responses for the SiNP treatment. Primary human lymphocytes are used to assess genotoxicity recommended by OECD guidelines while erythrocytes are used to assess hemolytic activity. The engineered silica nanoparticles are not able to produce radical species, to alter the mitochondrial membrane potential, and induce any adverse effects on cell proliferation. The colony formation ability of HuH-7 hepatoblastoma cells was not affected following the SiNP treatment. Furthermore, SiNPs do not induce hemolysis of red blood cells and are not genotoxic. These findings suggest that SiNPs regardless of the size, amount, and incubation time are biologically safe vehicles to deliver drugs or genes to the liver. • Engineered silica nanoparticles (SiNP) are dispersed in DMEM. • Biological responses of HuH-7, SK-HEP-1, primary human lymphocytes and erythrocytes treated with SiNPs are evaluated. • The SiNPs do not alter the mitochondrial membrane potential and induce any adverse effects on cell proliferation and cell cycle. • The colony formation capacity of cancer cells is not affected. • SiNPs regardless of the size, amount, and incubation time are biosafe vehicles to deliver drugs or genes to the liver. [ABSTRACT FROM AUTHOR]

Geranylgeranyl acetone (GGA) protects against various types of cell damages by upregulating heat shock proteins. We investigated whether GGA protects neuronal cells from cell death induced by oxidative stress. Glutamate exposure was lethal to HT-22 cells which comprise a neuronal line derived from mouse hippocampus. This configuration is often used as a model for hippocampus neurodegeneration in vitro. In the present study, GGA protected HT-22 cells from glutamate-induced oxidative stress. GGA pretreatment did not induce heat shock proteins (Hsps). Moreover, reactive oxygen species increased to the same extent in both GGA-pretreated and untreated cells exposed to glutamate. In contrast, glutamate exposure and GGA pretreatment increased mitochondrial membrane potential. However, increases in intracellular Ca2+ concentration were inhibited by GGA pretreatment. In addition, the increase of phosphorylated ERKs by the glutamate exposure was inhibited by GGA pretreatment. These findings suggest that GGA protects HT-22 cells from glutamate-provoked cell death without Hsp induction and that the mitochondrial calcium buffering capacity plays an important role in this protective effect. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a progressive neurodegenerative disease characterized by the selective loss of dopaminergic neurons in the nigrostriatal pathway. The lipophile 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) can cross the blood-brain barrier and is subsequently metabolized into toxic1-methyl-4-phenylpyridine (MPP(+) ), which causes mitochondrial dysfunction and the selective cell death of dopaminergic neurons. The present article reports the neuroprotective effects of silibinin in a murine MPTP model of PD. The flavonoid silibinin is the major active constituent of silymarin, an extract of milk thistle seeds, and is known to have hepatoprotective, anticancer, antioxidative, and neuroprotective effects. In the present study, silibinin effectively attenuated motor deficit and dopaminergic neuronal loss caused by MPTP. Furthermore, in vitro study confirmed that silibinin protects primary cultured neurons against MPP(+) -induced cell death and mitochondrial membrane disruption. The findings of the present study indicate that silibinin has neuroprotective effects in MPTP-induced models of PD rather than antioxidative or anti-inflammatory effects and that the neuroprotection afforded might be mediated by the stabilization of mitochondrial membrane potential. Furthermore, these findings suggest that silibinin protects mitochondria in MPTP-induced PD models and that it offers a starting point for the development of treatments that ameliorate the symptoms of PD., (© 2015 Wiley Periodicals, Inc.)