Indium/Gallium Maltolate Effects on Human Breast Carcinoma Cells: In Vitro Investigation on Cytotoxicity and Synergism with Mitoxantrone.
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ABSTRACT:
SUBMITTER: Merli D
PROVIDER: S-EPMC6044947 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Copper indium gallium diselenide-based technology provides the most efficient solar energy conversion among all thin-film photovoltaic devices. This is possible due to engineered gallium depth gradients and alkali extrinsic doping. Sodium is well known to impede interdiffusion of indium and gallium in polycrystalline Cu(In,Ga)Se2 films, thus influencing the gallium depth distribution. Here, however, sodium is shown to have the opposite effect in monocrystalline gallium-free CuInSe2 grown on GaAs substrates. Gallium in-diffusion from the substrates is enhanced when sodium is incorporated into the film, leading to Cu(In,Ga)Se2 and Cu(In,Ga)3Se5 phase formation. These results show that sodium does not decrease per se indium and gallium interdiffusion. Instead, it is suggested that sodium promotes indium and gallium intragrain diffusion, while it hinders intergrain diffusion by segregating at grain boundaries. The deeper understanding of dopant-mediated atomic diffusion mechanisms should lead to more effective chemical and electrical passivation strategies, and more efficient solar cells.
| S-EPMC5827571 | biostudies-literature
Project description:New drugs are needed for glioblastoma, an aggressive brain tumor with a dismal prognosis. We recently reported that gallium maltolate (GaM) retards the growth of glioblastoma in a rat orthotopic brain tumor model by inhibiting mitochondrial function and iron-dependent ribonucleotide reductase (RR). However, GaM's mechanism of action at the mitochondrial level is not known. Given the interaction between gallium and iron metabolism, we hypothesized that gallium might target iron-sulfur (Fe-S) cluster-containing mitochondrial proteins. Using Extracellular Flux Analyzer technology, we confirmed that after a 24-h incubation, GaM 50 ?mol/L inhibited glioblastoma cell growth by <10% but inhibited cellular oxygen consumption rate by 44% and abrogated mitochondrial reserve capacity. GaM blocked mitochondrial complex I activity and produced a 2.9-fold increase in cellular ROS. NMR spectroscopy revealed that gallium binds to IscU, the bacterial scaffold protein for Fe-S cluster assembly and stabilizes its folded state. Gallium inhibited the rate of in vitro cluster assembly catalyzed by bacterial cysteine desulfurase in a reaction mixture containing IscU, Fe (II), DTT, and L-cysteine. Metformin, a complex I inhibitor, enhanced GaM's inhibition of complex I, further increased cellular ROS levels, and synergistically enhanced GaM's cytotoxicity in glioblastoma cells in 2-D and 3-D cultures. Metformin did not affect GaM action on cellular iron uptake or transferrin receptor1 expression nor did it enhance the cytotoxicity of the RR inhibitor Didox. Our results show that GaM inhibits complex I by disrupting iron-sulfur cluster assembly and that its cytotoxicity can be synergistically enhanced by metformin through combined action on complex I.
| S-EPMC7197450 | biostudies-literature
Project description:Indium-containing particles (ICPs) are used extensively in the microelectronics industry. Pulmonary toxicity is observed after inhalation exposure to ICPs; however, the mechanism(s) of pathogenesis is unclear. ICPs are insoluble at physiological pH and are initially engulfed by alveolar macrophages (and likely airway epithelial cells). We hypothesized that uptake of ICPs by macrophages followed by phagolysosomal acidification results in the solubilization of ICPs into cytotoxic indium ions. To address this, we characterized the in vitro cytotoxicity of indium phosphide (InP) or indium tin oxide (ITO) particles with macrophages (RAW cells) and lung-derived epithelial (LA-4) cells at 24h using metabolic (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide) and membrane integrity (lactate dehydrogenase) assays. InP and ITO were readily phagocytosed by RAW and LA-4 cells; however, the particles were much more cytotoxic to RAW cells and cytotoxicity was dose dependent. Treatment of RAW cells with cytochalasin D (CytoD) blocked particle phagocytosis and reduced cytotoxicity. Treatment of RAW cells with bafilomycin A1, a specific inhibitor of phagolysosomal acidification, also reduced cytotoxicity but did not block particle uptake. Based on direct indium measurements, the concentration of ionic indium was increased in culture medium from RAW but not LA-4 cells following 24-h treatment with particles. Ionic indium derived from RAW cells was significantly reduced by treatment with CytoD. These data implicate macrophage uptake and solubilization of InP and ITO via phagolysosomal acidification as requisite for particle-induced cytotoxicity and the release of indium ions. This may apply to other ICPs and strongly supports the notion that ICPs require solubilization in order to be toxic.
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Project description:BackgroundGallium has demonstrated strong anti-inflammatory activity in numerous animal studies, and has also demonstrated direct antiviral activity against the influenza A H1N1 virus and the human immunodeficiency virus (HIV). Gallium maltolate (GaM), a small metal-organic coordination complex, has been tested in several Phase 1 clinical trials, in which no dose-limiting or other serious toxicity was reported, even at high daily oral doses for several months at a time. For these reasons, GaM may be considered a potential candidate to treat coronavirus disease 2019 (COVID-19), which is caused by the SARS-CoV-2 virus and can result in severe, sometimes lethal, inflammatory reactions. In this study, we assessed the ability of GaM to inhibit the replication of SARS-CoV-2 in a culture of Vero E6 cells.MethodsThe efficacy of GaM in inhibiting the replication of SARS-CoV-2 was determined in a screening assay using cultured Vero E6 cells. The cytotoxicity of GaM in uninfected cells was determined using the Cell Counting Kit-8 (CCK-8) colorimetric assay.ResultsThe results showed that GaM inhibits viral replication in a dose-dependent manner, with the concentration that inhibits replication by 50% (EC50) being about 14 µM. No cytotoxicity was observed at concentrations up to at least 200 µM.ConclusionThe in vitro activity of GaM against SARS-CoV-2, together with GaM's known anti-inflammatory activity, provide justification for testing GaM in COVID-19 patients.
| S-EPMC7768870 | biostudies-literature
Project description:Distal limb wounds are common injuries sustained by horses and their healing is fraught with complications due to equine anatomy, prevalence of infection, and challenges associated with wound management. Gallium is a semi-metallic element that has been shown to possess antimicrobial properties and aid in wound healing in various preclinical models. The effects of Gallium have not been studied in equine wound healing. Therefore, the objective of this study was to compare healing rates between gallium-treated and untreated wounds of equine distal limbs and to demonstrate the antimicrobial effects of gallium on wounds inoculated with S. aureus. Using an established model of equine wound healing we demonstrated beneficial effects of 0.5% topical gallium maltolate on equine wound healing. Specifically we documented reduced healing times, reduced bioburden, and reduced formation of exuberant granulation tissue in wounds treated with gallium maltolate as compared with untreated wounds. Gallium appeared to exert its beneficial effects via its well-described antimicrobial actions as well as by altering the expression of specific genes known to be involved in wound healing of horses and other animals. Specifically, gallium maltolate appeared to increase expression of transforming growth factor-? in both infected and un-infected wounds. Further work is needed to document the effects of gallium on naturally occurring equine wounds and to compare the effects of gallium with other wound treatment options. These data, however, suggest that gallium may be an attractive and novel means of improving equine distal limb wound healing.
| S-EPMC7304909 | biostudies-literature
Project description:In recent years the use of natural dietary antioxidants to minimize the cytotoxicity and the damage induced in normal tissues by antitumor agents is gaining consideration. In literature, it is reported that vitamin C exhibits some degree of antineoplastic activity whereas Mitoxantrone (MTZ) is a synthetic anti-cancer drug with significant clinical effectiveness in the treatment of human malignancies but with severe side effects. Therefore, we have investigated the effect of vitamin C alone or combined with MTZ on MDA-MB231 and MCF7 human breast cancer cell lines to analyze their dose-effect on the tumor cellular growth, cellular death, cell cycle and cell signaling. Our results have evidenced that there is a dose-dependence on the inhibition of the breast carcinoma cell lines, MCF7 and MDA-MB231, treated with vitamin C and MTZ. Moreover, their combination induces: i) a cytotoxic effect by apoptotic death, ii) a mild G2/M elongation and iii) H2AX and mild PI3K activation. Hence, the formulation of vitamin C with MTZ induces a higher cytotoxicity level on tumor cells compared to a disjointed treatment. We have also found that the vitamin C enhances the MTZ effect allowing the utilization of lower chemotherapic concentrations in comparison to the single treatments.
| S-EPMC4274052 | biostudies-literature
Project description:Because of tunable bandgap and high carrier mobility, ternary III-V nanowires (NWs) have demonstrated enormous potential for advanced applications. However, the synthesis of large-scale and highly-crystalline InxGa1-xSb NWs is still a challenge. Here, we achieve high-density and crystalline stoichiometric InxGa1-xSb (0.09 < x < 0.28) NWs on amorphous substrates with the uniform phase-purity and <110 >-orientation via chemical vapor deposition. The as-prepared NWs show excellent electrical and optoelectronic characteristics, including the high hole mobility (i.e. 463 cm2 V-1 s-1 for In0.09Ga0.91Sb NWs) as well as broadband and ultrafast photoresponse over the visible and infrared optical communication region (1550 nm). Specifically, the In0.28Ga0.72Sb NW device yields efficient rise and decay times down to 38 and 53 μs, respectively, along with the responsivity of 6000 A W-1 and external quantum efficiency of 4.8 × 106 % towards 1550 nm regime. High-performance NW parallel-arrayed devices can also be fabricated to illustrate their large-scale device integrability for next-generation, ultrafast, high-responsivity and broadband photodetectors.
| S-EPMC6458123 | biostudies-literature
Project description:Recycling of the semiconductor material copper indium gallium diselenide (CIGS) is important to ensure a future supply of indium and gallium, which are relatively rare and therefore expensive elements. As a continuation of our previous work, where we recycled high purity selenium from CIGS waste materials, we now show that copper and indium can be recycled by electrodeposition from hydrochloric acid solutions of dissolved selenium-depleted material. Suitable potentials for the reduction of copper and indium were determined to be -0.5 V and -0.9 V (versus the Ag/AgCl reference electrode), respectively, using cyclic voltammetry. Electrodeposition of first copper and then indium from a solution containing the dissolved residue from the selenium separation and ammonium chloride in 1 M HCl gave a copper yield of 100.1 ± 0.5% and an indium yield of 98.1 ± 2.5%. The separated copper and indium fractions contained no significant contamination of the other elements. Gallium remained in solution together with a small amount of indium after the separation of copper and indium and has to be recovered by an alternative method since electrowinning from the chloride-rich acid solution was not effective.
| S-EPMC4549614 | biostudies-other
Project description:III-nitride materials have been linked with a vast number of exciting applications from power electronics to solar cells. Herein, polycrystalline InN, GaN and systematically controlled InxGa1-xN composite thin films are fabricated on FTO glass by a facile, low-cost and scalable aerosol assisted chemical vapor deposition technique. Variation of the indium content in the composite films leads to a dramatic shift in the optical absorbance properties, which correlates with the band edges shifting between those of GaN to InN. Moreover, the photoelectrochemical properties are shown to vary with indium content, with the 50% indium composite having an external quantum efficiency of around 8%. Whilst the overall photocurrent is found to be low, the photocurrent stability is shown to be excellent, with little degradation seen over 1?hour. These findings demonstrate a new and low-cost method for fabricating polycrystalline III-nitrides, which have a range of interesting properties that are highly sought after for many applications.
| S-EPMC6381210 | biostudies-literature
Project description:Nanostructure (NS) InGaN crystals were grown on carbon nanotubes (CNTs) using metalorganic chemical vapor deposition. The NS-InGaN crystals, grown on a ~5-?m-long CNT/Si template, were estimated to be ~100-270?nm in size. Transmission electron microscope examinations revealed that single-crystalline InGaN NSs were formed with different crystal facets. The observed green (~500?nm) cathodoluminescence (CL) emission was consistent with the surface image of the NS-InGaN crystallites, indicating excellent optical properties of the InGaN NSs on CNTs. Moreover, the CL spectrum of InGaN NSs showed a broad emission band from 490 to 600?nm. Based on these results, we believe that InGaN NSs grown on CNTs could aid in overcoming the green gap in LED technologies.
| S-EPMC4644961 | biostudies-other