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Biological Research Mar 2019Hypoxia microenvironment plays a crucial role during tumor progression and it tends to exhibit poor prognosis and make resistant to various conventional therapies....
BACKGROUND/AIMS
Hypoxia microenvironment plays a crucial role during tumor progression and it tends to exhibit poor prognosis and make resistant to various conventional therapies. HIF-1α acts as an important transcriptional regulator directly or indirectly associated with genes involved in cell proliferation, angiogenesis, apoptosis and energy metabolism during tumor progression in hypoxic microenvironment. This study was aimed to investigate the expression pattern of the hypoxia associated genes and their association during breast cancer progression under hypoxic microenvironment in breast cancer cells.
METHODS
Cell proliferation in MCF-7 and MDA-MB-231 cell lines treated with different concentration of CoCl was analyzed by MTT assay. Flow cytometry was performed to check cell cycle distribution, whereas cell morphology was examined by phase contrast microscopy in both the cells during hypoxia induction. Expression of hypoxia associated genes HIF-1α, VEGF, p53 and BAX were determined by semiquantitative RT-PCR and real-time PCR. Western blotting was performed to detect the expression at protein level.
RESULTS
Our study revealed that cell proliferation in CoCl treated breast cancer cells were concentration dependent and varies with different cell types, further increase in CoCl concentration leads to apoptotic cell death. Further, accumulation of p53 protein in response to hypoxia as compare to normoxia showed that induction of p53 in breast cancer cells is HIF-1α dependent. HIF-1α dependent BAX expression during hypoxia revealed that after certain extent of hypoxia induction, over expression of BAX conquers the effect of anti-apoptotic proteins and ultimately leads to apoptosis in breast cancer cells.
CONCLUSION
In conclusion our results clearly indicate that CoCl simulated hypoxia induce the accumulation of HIF-1α protein and alter the expression of hypoxia associated genes involved in angiogenesis and apoptosis.
Topics: Apoptosis; Blotting, Western; Cell Hypoxia; Cell Line, Tumor; Cell Proliferation; Cobalt; Flow Cytometry; Gene Expression Regulation, Neoplastic; Humans; MCF-7 Cells; Transfection
PubMed: 30876462
DOI: 10.1186/s40659-019-0221-z -
IARC Monographs on the Evaluation of... 1991
Review
Topics: Air Pollutants, Occupational; Alloys; Animals; Carcinogenicity Tests; Cobalt; Environmental Exposure; Humans; Metallurgy; Mutagenicity Tests; Organometallic Compounds
PubMed: 1960848
DOI: No ID Found -
Bioengineered Mar 2022Cobalt is the main component of metal prostheses in hip arthroplasty. Studies have shown that metal particles mainly composed of cobalt nanoparticles (CoNPs) can cause...
Cobalt is the main component of metal prostheses in hip arthroplasty. Studies have shown that metal particles mainly composed of cobalt nanoparticles (CoNPs) can cause systemic and local toxic reactions due to various physical and chemical factors. Therefore, elucidating the underlying mechanisms of metal prosthesis action, coupled with identification of effective detoxification drugs are imperative to minimizing postoperative complications and prolonging the service life of these clinical tools. In this study, we treated Balb/3T3 mouse fibroblast cell line with CoNPs and ferrostatin-1, then measured cell viability via the CCK-8 assay. Next, we determined levels of reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH), cobalt and iron contents, as well as glutathione peroxidase 4 (GPX4), and solute carrier family 7 member 11 (SLC7A11) expression in each group. Finally, we employed transmission electron microscopy (TEM) to detect changes in the ultrastructure of each group of cells. Exposure of cells to CoNPs significantly suppressed their viability, and downregulated expression of GSH, GPX4, and SLC7A11 proteins. Conversely, this treatment mediated a significant increase in ROS, MDA, cobalt, and iron levels in the cells. TEM images revealed a marked increase in density of the mitochondrial membrane of cells in the CoNPs group, while the outer membrane was broken. Notably, treatment with ferroptosis inhibitor Ferrostatin-1 alleviated the cytotoxic response caused by CoNPs. These findings suggest that CoNP-induced cytotoxicity may be closely related to ferroptosis, indicating that inhibition of ferroptosis is a potential therapeutic strategy for reducing CoNP toxicity.
Topics: Animals; Cobalt; Cyclohexylamines; Ferroptosis; Iron; Mice; Nanoparticles; Phenylenediamines; Reactive Oxygen Species
PubMed: 35200065
DOI: 10.1080/21655979.2022.2042143 -
Inorganic Chemistry Apr 2022This paper describes the synthesis and reactivity studies of three cobalt complexes bearing aminophenol-derived ligands without nitrogen substitution: Co(APH)(AP) (),...
This paper describes the synthesis and reactivity studies of three cobalt complexes bearing aminophenol-derived ligands without nitrogen substitution: Co(APH)(AP) (), Co(APH)(AP)(μ-BAP) (), and Co(AP) (), where APH = 2-amino-4,6-di--butylphenol, AP = 2-amino-4,6-di--butylphenolate, and μ-BAP = bridging 2-amido-4,6-di--butylphenolate. Stoichiometric reactivity studies of these well-defined complexes demonstrate the catalytic competency of both cobalt(II) and cobalt(III) complexes in the aerobic oxidative cyclization of APH with -butylisonitrile. Reactions with O reveal the aerobic oxidation of the cobalt(II) complex to generate the cobalt(III) species and . UV-visible time-course studies and electron paramagnetic resonance spectroscopy indicate that this oxidation proceeds through a ligand-based radical intermediate. These studies represent the first example of well-defined cobalt aminophenol complexes that participate in catalytic aerobic oxidation reactions and highlight a key role for a ligand radical in the oxidation sequence.
Topics: Catalysis; Cobalt; Electron Spin Resonance Spectroscopy; Ligands; Oxidation-Reduction
PubMed: 35414172
DOI: 10.1021/acs.inorgchem.1c03686 -
Cartilage Dec 2021Cobalt and chromium (CoCr) ions from metal implants are released into the joint due to biotribocorrosion, inducing apoptosis and altering gene expression in various cell...
OBJECTIVE
Cobalt and chromium (CoCr) ions from metal implants are released into the joint due to biotribocorrosion, inducing apoptosis and altering gene expression in various cell types. Here, we asked whether CoCr ions concentration-dependently changed viability, transcriptional activity, and inflammatory response in human articular chondrocytes.
DESIGN
Human articular chondrocytes were exposed to Co (1.02-16.33 ppm) and Cr (0.42-6.66 ppm) ions and cell viability and early/late apoptosis (annexin V and 7-AAD) were assessed in 2-dimensional cell cultures using the XTT assay and flow cytometry, respectively. Changes in chondrocyte morphology were assessed using transmitted light microscopy. The effects of CoCr ions on transcriptional activity of chondrocytes were evaluated by quantitative polymerase chain reaction (qPCR). The inflammatory responses were determined by measuring the levels of released pro-inflammatory cytokines (interleukin-1β [IL-1β], IL-6, IL-8, and tumor necrosis factor-α [TNF-α]).
RESULTS
CoCr ions concentration-dependently reduced metabolic activity and induced early and late apoptosis after 24 hours in culture. After 72 hours, the majority of chondrocytes (>90%) were apoptotic at the highest concentrations of CoCr ions (16.33/6/66 ppm). expression was concentration-dependently enhanced, whereas expression of linearly decreased after 24 hours. IL-8 release was enhanced proportionally to CoCr ions levels, whereas IL-1β, IL-6, and TNF-α levels were not affected by the treatments.
CONCLUSIONS
CoCr ions showed concentration- and time-dependent effects on articular chondrocytes. Fractions of apoptotic articular chondrocytes were proportional to CoCr ion concentrations. In addition, metabolic activity and expression of chondrocyte-specific genes were decreased by CoCr ions. Furthermore, exposure to CoCr ions caused a release of pro-inflammatory cytokines.
Topics: Cells, Cultured; Chondrocytes; Chromium; Cobalt; Humans; Ions
PubMed: 31779468
DOI: 10.1177/1947603519889389 -
Clinical Chemistry and Laboratory... Jan 2013Individuals with advanced hip disease suffer from pain, impaired hip function, and decreased quality of life. Roughly one million metal-on-metal (MoM) hip prostheses... (Review)
Review
Individuals with advanced hip disease suffer from pain, impaired hip function, and decreased quality of life. Roughly one million metal-on-metal (MoM) hip prostheses have been implanted worldwide in order to ameliorate these issues. While most MoM hip replacements are successful, some patients suffer from serious adverse effects secondary to the release of metal debris due to implant wear and corrosion. MoM hip prostheses are comprised predominantly of cobalt and chromium, and the serum concentration of these metal ions has been shown to correlate with both implant wear and the accumulation of metal debris in the periprosthetic tissue. Consequently, measurement of cobalt and chromium concentrations may be useful in the assessment of implant function and the potential for adverse effects in the follow-up of patients with MoM hip prostheses. The purpose of this Mini Review is to describe the adverse biological consequences of metal release from hip prostheses, provide an overview of the clinical utility of cobalt and chromium measurement and the current recommendations for testing, and alert laboratorians and physicians to the many challenges associated with measuring these metal ions.
Topics: Chromium; Clinical Laboratory Techniques; Cobalt; Hip Prosthesis; Humans
PubMed: 23023696
DOI: 10.1515/cclm-2012-0492 -
Toxicological Sciences : An Official... Apr 2020Based on the wide use of cobalt substances in a range of important technologies, it has become important to predict the toxicological properties of new or lesser-studied... (Comparative Study)
Comparative Study
Based on the wide use of cobalt substances in a range of important technologies, it has become important to predict the toxicological properties of new or lesser-studied substances as accurately as possible. We studied a group of 6 cobalt substances with inorganic ligands, which were tested for their bioaccessibility (surrogate measure of bioavailability) through in vitro bioelution in simulated gastric and intestinal fluids. Representatives of the group also underwent in vivo blood kinetics and mass balance tests, and both oral acute and repeated dose toxicity (RDT) testing. We were able to show a good correlation between high in vitro bioaccessibility with high in vivo bioavailability and subsequent high in vivo toxicity; consequently, low in vitro bioaccessibility correlated well with low in vivo bioavailability and low in vivo toxicity. In vitro bioelution in simulated gastric fluid was the most precise predictor of the difference in the oral RDT lowest observed adverse effect levels of 2 compounds representing the highly and poorly bioaccessible subset of substances. The 2 compounds cobalt dichloride hexahydrate and tricobalt tetraoxide differed by a factor of 440 in their in vitro bioaccessibility and by a factor of 310 in their RDT lowest observed adverse effect level. In summary, this set of studies shows that solubility, specifically in vitro bioelution in simulated gastric fluid, is a good, yet conservative, predictor of in vivo bioavailability and oral systemic toxicity of inorganic cobalt substances. Bioelution data are therefore an invaluable tool for grouping and read across of cobalt substances for hazard and risk assessment.
Topics: Administration, Oral; Animals; Biological Availability; Cobalt; Female; Gastric Juice; Injections, Intravenous; Intestinal Secretions; Male; Oxides; Rats, Sprague-Dawley; Risk Assessment; Solubility; Toxicokinetics
PubMed: 32058562
DOI: 10.1093/toxsci/kfz249 -
Scientific Reports Aug 2022Detection of heavy transition metals is of importance protecting humans and the environment from their toxicity. Amongst them, copper(II) and cobalt(II) need more...
Detection of heavy transition metals is of importance protecting humans and the environment from their toxicity. Amongst them, copper(II) and cobalt(II) need more attention due to their wide applications in industry, in which exposures with excess amounts of them cause heathy concerns. Hence, fast and efficient distinguishing copper(II) and cobalt(II) could be worthy. While electrochemical approaches could determine these cations, expensive instrumentation and time-consuming analysis are significant drawbacks, leading to concentrations on spectroscopic and colorimetric pathways. Herein, graphene quantum dot was modified with Eriochrome Black T (EBT) to generate a novel sensor with the ability of sensing mentioned cations. This new nanocompound demonstrated new optical properties when complexed with cobalt(II) in natural pH, and copper(II) in acidic media. Both cations successfully were detected by the new nanosensor through revealing distinct spectroscopic signals. Moreover, cobalt(II) was distinguished by this sensor colorimetrical, appearing green solution. Linear ranges of cobalt(II) and copper(II) were obtained as 0.02-0.08 M and 0.015-0.2 M, with the limit of detections 0.014 and 0.018 M, respectively.
Topics: Azo Compounds; Cobalt; Copper; Graphite; Humans; Quantum Dots
PubMed: 35915314
DOI: 10.1038/s41598-022-17616-y -
Organic Letters Feb 2021A cobalt-catalyzed method for the C(sp)-C(sp) Suzuki-Miyaura cross coupling of aryl boronic esters and alkyl bromides is described. Cobalt-ligand combinations were...
A cobalt-catalyzed method for the C(sp)-C(sp) Suzuki-Miyaura cross coupling of aryl boronic esters and alkyl bromides is described. Cobalt-ligand combinations were assayed with high-throughput experimentation, and cobalt(II) sources with -,'-dimethylcyclohexane-1,2-diamine (DMCyDA, L) produced optimal yield and selectivity. The scope of this transformation encompassed steric and electronic diversity on the aryl boronate nucleophile as well as various levels of branching and synthetically valuable functionality on the electrophile. Radical trap experiments support the formation of electrophile-derived radicals during catalysis.
Topics: Bromides; Catalysis; Cobalt; Diamines; Esters; Ligands; Molecular Structure
PubMed: 32996312
DOI: 10.1021/acs.orglett.0c02934 -
International Journal of Molecular... May 2022The combination of the sonochemical activation of Ni(NO) and Co(NO) in the presence of Fe(NO) and polyethylene glycol and consecutive heat treatment of the formed metal...
The combination of the sonochemical activation of Ni(NO) and Co(NO) in the presence of Fe(NO) and polyethylene glycol and consecutive heat treatment of the formed metal hydroxides offers a cheap and efficient method for the preparation of nickel ferrite and cobalt ferrite magnetic nanoparticles, which can be successfully applied in the selective capture of fluorescently derivatized N-glycans from human serum. XRD measurement revealed that, besides the ferrite phase, nickel and cobalt oxides also form during heat treatment. The amount of simple metal oxides can be well controlled by the temperature of the heat treatment, since increasing temperature yielded higher spinel content. For both nickel and cobalt, the best heat treatment temperature was found to be 673 K, where the samples contained 84.1% nickel ferrite, and in the case of cobalt, almost pure (99.6%) cobalt ferrite could be prepared. FT-IR and zeta potential measurements indicated the presence of surface OH groups, which aided in the dispersion of the particles in water and, in addition, can promote the adsorption of polar compounds. The practical applicability of the magnetic nanopowders was demonstrated in the purification of fluorescently derivatized N-glycans (from human serum). Cobalt ferrite was found to be the most effective. Owing to the easy preparation and the simplicity of the magnetic separation the pure cobalt ferrite, magnetic nanoparticles could be efficient tools for the selective enrichment of serum N-glycans in HPLC measurements.
Topics: Cobalt; Ferric Compounds; Humans; Magnetite Nanoparticles; Nickel; Oxides; Spectroscopy, Fourier Transform Infrared
PubMed: 35563468
DOI: 10.3390/ijms23095081