ABSTRACT
BACKGROUND B-cell lymphoma 2 (BCL-2) ovarian killer (BOK) is a Bcl-2 family member with sequence homology to pro-apoptotic BAX and BAK, but its physiological and pathological roles remain largely unclear. Exposure of cells to cadmium may cause DNA damage, decrease DNA repair capacity, and increase genomic instability. MATERIAL AND METHODS The present study investigated the effects of BOK on the toxicity of cadmium chloride (CdCl2) to human bronchial epithelial (16HBE) cells. We constructed BOK over-expressing (16HBE-BOK) cells and BOK knockdown (16HBE-shBOK) cells using the BOK-ORF plasmid and BOK-siRNA. qRT-PCR for BOK mRNA expression. We used Trypan blue exclusion assay for cell growth, MTT colorimetric assays for cells inhibition rate, and Comet assays for detecting damaged DNA. RESULTS CdCl2, at various concentrations and exposure times, increased BOK mRNA. 16HBE-BOK cells (BOK over-expressing) proliferated more than 16HBE cells after 72 h; 16HBE-shBOK (BOK knockdown) cells proliferated less. In addition, BOK deficiency enhanced cell death induced by CdCl2. Similarly, CdCl2- and H2O2-induced DNA damage was greater in BOK-deficient cells. CONCLUSIONS These findings support a role for BOK in CdCl2-induced DNA damage and cell death.
Subject(s)
Cadmium Chloride/toxicity , Epithelial Cells/drug effects , Lung/drug effects , Proto-Oncogene Proteins c-bcl-2/metabolism , Apoptosis/drug effects , Bronchi/drug effects , Bronchi/metabolism , Bronchi/pathology , Cell Cycle/drug effects , Cell Death/drug effects , Cell Line , DNA Damage , Epithelial Cells/metabolism , Epithelial Cells/pathology , Humans , Lung/metabolism , Lung/pathology , RNA, Messenger/metabolismABSTRACT
The success of arsenic trioxide (ATO) in treatment of acute promyelocytic leukemia (APL) attracts a great deal of attention to researchers to explore its activity of anti-leukemia. However, ATO has unavailable effect on chronic myeloid leukemia (CML), especially multidrug resistant (MDR)-CML, unless using high concentration. Realgar (As(4)S(4)) has been employed in Chinese traditional medicine for 1500 years. Research evidences confirmed realgar has similar effect on treating with APL as ATO, but the problem of large dose and long period in the CML/MDR-CML treatment still exist. By using a microbial leaching process with Acidithiobacillus ferrooxidans, we obtained realgar transforming solution (RTS) which showed significantly higher extent in inhibiting CML cell line K562 and MDR-CML cell line K562/ADM, and then trigger apoptosis. Both K562 and K562/ADM showed arsenic-dose-dependent effect on RTS. Interestingly, the overexpression of MDR1 mRNA and P-glucoprotein (P-gp) in K562/ADM cells were down-regulated by RTS, where there are no obvious effects on ATO and realgar and arsenic can be subsequently accumulated in K562/ADM cells efficiently. The intracellular accumulation of arsenic in K562/ADM cells treated with RTS for 4 h was 2-fold and 16-folds higher than those treated with realgar or ATO. Meanwhile, Western blot analysis of AQP9, the main transporter of arsenic, was increased by RTS treatment particularly in K562/ADM. Thus, these results suggested that the effect from a certain arsenical or a variety of arsenicals in RTS might be a promising candidate both for treating CML/MDR-CML alone and as combinations with currently used anti-CML/MDR-CML drug, although arsenical forms in RTS are undefined.
Subject(s)
Antineoplastic Agents/pharmacology , Arsenicals/pharmacology , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Oxides/pharmacology , Sulfides/pharmacology , ATP Binding Cassette Transporter, Subfamily B , ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics , ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , Acidithiobacillus/metabolism , Apoptosis/drug effects , Aquaporins/genetics , Arsenic Trioxide , Arsenicals/metabolism , Cell Cycle/drug effects , Drug Resistance, Multiple , Drug Resistance, Neoplasm , Humans , K562 Cells , RNA, Messenger/metabolism , Solutions , Sulfides/metabolismABSTRACT
Phenylpropanoid amides of octopamine (OA) 1a-1e and dopamine (DA) 2a-2e were synthesised and the structure-activity relationships (SARs) for antioxidant and tyrosinase inhibition activities were analysed. Among synthesised compounds, 2c, which contains two catechol moieties, exhibited the most DPPH radical-scavenging activity (EC(50)=16.2 ± 2.4 µM), and 1d exhibited significant tyrosinase inhibitory activity (IC(50)=5.3 ± 1.8 µM). Interestingly, with the same acid moiety, OA derivatives showed more inhibitory effect on tyrosinase than did compounds derived from DA, whereas DA derivatives were found to have higher antioxidant activity than compounds derived from OA. The relationship between their structures and their potencies, demonstrated in the current study, will be useful for the design of optimal agents.
Subject(s)
Antioxidants/chemical synthesis , Dopamine/chemical synthesis , Enzyme Inhibitors/chemical synthesis , Monophenol Monooxygenase/antagonists & inhibitors , Octopamine/chemical synthesis , Antioxidants/chemistry , Antioxidants/pharmacology , Dopamine/chemistry , Dopamine/pharmacology , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Inhibitory Concentration 50 , Molecular Structure , Monophenol Monooxygenase/metabolism , Octopamine/chemistry , Octopamine/pharmacology , Structure-Activity RelationshipABSTRACT
Magnetite nanocrystal has been extensively used in biomedical field. Currently, an interesting alternative to synthetic magnetic Fe3O4 nanoparticles, called magnetosome, has been found in magnetotactic bacteria. It has been reported that Acidithiobacillus ferrooxidans (At. ferrooxidans) has a potential to synthesize magnetosome. In this study, transmission electron microscope (TEM) was used to analyze the magnetite particles in At. ferrooxidans BY-3. The magnetosomes formed by this bacterium were isolated by a method combining ultracentrifugation and magnetic separation. Crystalline phase and surface functional group of the magnetosomes were investigated by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR), respectively. Biocompatibility of the magnetosomes was systematically evaluated at various concentrations (0.5, 1.0, 2.0 and 4.0mg/ml). MTT test, hemolysis assay and Micronucleus Test were carried out to evaluate in vitro cytotoxicity, blood toxicity and genotoxicity of magnetosomes, respectively. Under these conditions, magnetosomes showed no cytotoxic, genotoxic and hemolytic effects up to 4.0mg/ml indicating good biocompatibility of these biological nanoparticles. These revealed that the magnetosomes might have a potential for biotechnological and biomedical applications in the future.
ABSTRACT
The characteristics of the bioleaching of realgar by Acidithiobacillus ferrooxidans BY-3 (A. ferrooxidans) were investigated in this work. We examined the effects of using ferrous iron and elemental sulfur as the sole and mixed energy sources on the bioleaching of realgar. Under all experimental conditions, A. ferrooxidans BY-3 significantly enhanced the dissolution of realgar. Moreover, arsenic was more efficiently leached using A. ferrooxidans BY-3 in the presence of ferrous iron than in other culture conditions. A high concentration of arsenic was observed in the absence of alternative energy sources. This concentration was higher than that in cultures with sulfur only and lower than that in cultures with ferrous iron and sulfur. Linear or nonlinear models best fit the experimental data; the nonlinear model exhibited the dual effects of dissolution and removal on the bioleaching of realgar, whereas the linear model only applied to situations of slow bioleaching rather than removal.
