Selenium is generally known as an antioxidant due to its presence in selenoproteins as selenocysteine, but it is also toxic. The toxic effects of selenium are, however, strictly concentration and ...chemical species dependent. One class of selenium compounds is a potent inhibitor of cell growth with remarkable tumor specificity. These redox active compounds are pro-oxidative and highly cytotoxic to tumor cells and are promising candidates to be used in chemotherapy against cancer. Herein we elaborate upon the major forms of dietary selenium compounds, their metabolic pathways, and their antioxidant and pro-oxidant potentials with emphasis on cytotoxic mechanisms. Relative cytotoxicity of inorganic selenite and organic selenocystine compounds to different cancer cells are presented as evidence to our perspective. Furthermore, new novel classes of selenium compounds specifically designed to target tumor cells are presented and the potential of selenium in modern oncology is extensively discussed.
Display omitted
•Astaxanthin (Ast) coated ZnO and CeO2 NPs were synthesized and characterized.•Ast:ZnO and Ast:CeO2 NPs shows the good absorbance band in UV region.•Ast:ZnO and Ast:CeO2 NPs were ...hexagonal rod shaped and small particles with network like structure.•Ast:ZnO and Ast:CeO2 NPs exhibited good inhibition zone against bacteria and fungi.
ZnO and CeO2 nanoparticles (NPs) are synthesized using Chamaecostus cuspidatus extract by greener route. Synthesized ZnO and CeO2 NPs were coated with astaxanthin as synthesized Ast:ZnO and Ast:CeO2 NPs retained the hexagonal wurtzite structure and cubic structure, which were confirmed by XRD studies. FESEM images revealed Ast:ZnO and Ast:CeO2 NPs were nano-rod and sphere-shaped structure. Chemical compositions were recognized by using EDAX analysis. FT-IR and Raman spectra confirmed the stretching bands for Ast:ZnO and Ast:CeO2 NPs. UV–VIS absorption spectra, the absorption edges peak was observed at 360 nm and 309 nm for Ast:ZnO and Ast:CeO2 NPs respectively. Antimicrobial activities were carried out against a set of bacterial and fungal strains for the AST: ZnO and Ast:CeO2 NPs using Chamaecostus cuspidatus leaf extract. Anticancer properties are studied with human breast cancer cell line (MCF 7) using Ast:ZnO and Ast:CeO2 NPs.
The unique character of selenium compounds, including sodium selenite and Se-methylselenocysteine (MSC), is that they exert cytotoxic effects on neoplastic cells, providing a great potential for ...treating cancer cells being highly resistant to cytostatic drugs. However, selenium treatment may affect microRNA (miRNA) expression as the pattern of circulating miRNAs changed in a placebo-controlled selenium supplement study. This necessitates exploring possible changes in the expression profiles of miRNAs. For this, miRNAs being critical for liver function were selected and their expression was measured in hepatocellular carcinoma (HLE and HLF) and cholangiocarcinoma cell lines (TFK-1 and HuH-28) using individual TaqMan MicroRNA Assays following selenite or MSC treatments. For establishing tolerable concentrations, IC
50
values were determined by performing SRB proliferation assays. The results revealed much lower IC
50
values for selenite (from 2.7 to 11.3 μM) compared to MSC (from 79.5 to 322.6 μM). The treatments resulted in cell line-dependent miRNA expression patterns, with all miRNAs found to show fold change differences; however, only a few of these changes were statistically different in treated cells compared to untreated cells below IC
50
. Namely, miR-199a in HLF, miR-143 in TFK-1 upon MSC treatment, miR-210 in HLF and TFK-1, miR-22, -24, -122, −143 in HLF upon selenite treatment. Fold change differences revealed that miR-122 with both selenium compounds, miR-199a with MSC and miR-22 with selenite were affected. The miRNAs showing minimal alterations included miR-125b and miR-194. In conclusion, our results revealed moderately altered miRNA expression in the cell lines (less alterations following MSC treatment), being miR-122, −199a the most affected and miR-125b, -194 the least altered miRNAs upon selenium treatment.
Kynurenine aminotransferase 1 (KYAT1 or CCBL1) plays a major role in Se-methylselenocysteine (MSC) metabolism. It is a bi-functional enzyme that catalyzes transamination and beta-elimination activity ...with a single substrate. KYAT1 produces methylselenol (CH
SeH) via β-elimination activities with MSC as a substrate. This methylated selenium compound is a major cytotoxic selenium metabolite, causing apoptosis in a wide variety of cancer cells. Methylselenol is volatile and possesses extraordinary nucleophilic properties. We herein describe a simple spectrophotometric assay by combining KYAT1 and thioredoxin reductase (TrxR) to detect CH
SeH in a coupled activity assay. The metabolite methylselenol and its oxidized form from MSC metabolism is utilized as a substrate for TrxR1 and this can be monitored spectroscopically at 340 nm. Our results show the feasibility of monitoring the β-elimination of KYAT1 by our assay and the results were compared to the previously described β-elimination assays measuring pyruvate. By using known inhibitors of KYAT1 and TrxR1, we further validated the respective reaction. Our data provide a simple but accurate method to determine the β-elimination activity of KYAT1, which is of importance for mechanistic studies of a highly interesting selenium compound.
Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer. PDAC has a dismal prognosis and an inherent resistance to cytostatic drugs. The lack of reliable experimental ...models is a severe limitation for drug development targeting PDAC. We have employed a whole tissue
ex vivo
culture model to explore the effect of redox-modulation by sodium selenite on the viability and growth of PDAC. Drug-resistant tumors are more vulnerable to redox-active selenium compounds because of high metabolic activity and redox imbalance. Sodium selenite efficiently and specifically reduced PDAC cell viability (p <0.02) (n=8) and decreased viable
de novo
tumor cell outgrowth (p<0.05) while preserving non-neoplastic tissues. Major cellular responses (damaged tumor cells > 90%, tumor regression grades III-IV according to Evans) were observed for sodium selenite concentrations between 15-30 µM. Moreover, selenium levels used in this study were significantly below the previously reported maximum tolerated dose for humans. Transcriptome data analysis revealed decreased expression of genes known to drive PDAC growth and metastatic potential (CEMIP, DDR2, PLOD2, P4HA1) while the cell death-inducing genes (ATF3, ACHE) were significantly upregulated (p<0.0001). In conclusion, we report that sodium selenite has an extraordinary efficacy and specificity against drug-resistant pancreatic cancer in an organotypic slice culture model. Our
ex vivo
organotypic tissue slice culture model can be used to test a variety of drug candidates for swift and reliable drug responses to individual PDAC cases.
A study on anti-bactericidal filter is carried out using electrospun polyacrylonitrile (PAN) nanofibres by incorporating different weight percentages of silver (Ag) nanoparticles. Dimethylformamide ...(DMF) plays dual role, as solvent for PAN and as reducing agent for the formation of Ag nanoparticles, and the Ag nanoparticles were characterized using UV-Visible Spectroscopy, X-ray diffraction, and transmission electron microscopy. Then, PAN solutions with Ag nanoparticles were electrospun to produce nanofibres. Areal density of nonwoven substrate, electrospinning time, and Ag% were taken as independent variables to design the experiment for the preparation of filter. Box-Behnken method has been used to derive the experimental plan and the filters were prepared according to the plan. Later, the developed filters were studied for bacterial filtration efficiency (BFE) as well as the anti-bactericidal activity against two commonly studied grampositive
S. aureus
and gram-negative
E. coli
bacteria. From the study, the developed Ag nanoparticle incorporated PAN electrospun nanofibre filters possess 99 % BFE with good anti-bactericidal activity, which enhances the potential application in protective mask.
Patient-derived tissue culture models are valuable tools to investigate drug effects and targeted treatment approaches. Resected tumor slices cultured ex vivo have recently gained interest in ...precision medicine, since they reflect the complex microenvironment of cancer tissue. In this study, we examined the treatment response to an internally developed ex vivo tissue culture model from pancreatic ductal adenocarcinoma (PDAC) and in vitro analysis. Seven PDAC tissues were cultured and subsequently treated with indole-3-pyruvic acid (IPA). IPA, which is known as an agonist of the aryl hydrocarbon receptor (AHR) pathway, has antioxidant properties. Genome-wide transcriptome sequencing analysis revealed activation of AHR pathway genes (CYP1A1 and CYP1B1,
≤ 0.05). Additionally, significant upregulation of AHR repressor genes AHRR and TiPARP was also observed (
≤ 0.05), which is indicative of the negative feedback loop activation of AHR pathway signaling. The overall transcriptomic response to IPA indicated that the tissues are biologically active and respond accordingly to exogenous treatment. Cell culture analysis confirmed the significant induction of selected AHR genes by IPA. A morphological examination of the paraffin-embedded formalin-fixed tissue did not show obvious signs of IPA treatment related to tumor cell damage. This study is a proof of concept that ex vivo patient-derived tissue models offer a valuable tool in precision medicine to monitor the effect of personalized treatments.
Despite progress in the treatment of non-visceral malignancies, the prognosis remains poor for malignancies of visceral organs and novel therapeutic approaches are urgently required. We evaluated a ...novel therapeutic regimen based on treatment with Se-methylselenocysteine (MSC) and concomitant tumor-specific induction of Kynurenine aminotransferase 1 (KYAT1) in hepatocellular carcinoma (HCC) cell lines, using either vector-based and/or lipid nanoparticle-mediated delivery of mRNA. Supplementation of MSC in KYAT1 overexpressed cells resulted in significantly increased cytotoxicity, due to ROS formation, as compared to MSC alone. Furthermore, microRNA antisense-targeted sites for miR122, known to be widely expressed in normal hepatocytes while downregulated in hepatocellular carcinoma, were added to specifically limit cytotoxicity in HCC cells, thereby limiting the off-target effects. KYAT1 expression was significantly reduced in cells with high levels of miR122 supporting the concept of miR-guided induction of tumor-specific cytotoxicity. The addition of alpha-ketoacid favored the production of methylselenol, enhancing the cytotoxic efficacy of MSC in HCC cells, with no effects on primary human hepatocytes. Altogether, the proposed regimen offers great potential to safely and specifically target hepatic tumors that are currently untreatable.
A multifunctional layer by layer nanocomposite air filter was fabricated by using electrospinning method. Polyacrylonitrile (PAN) nanofibers incorporated with silver nanoparticles (Ag NP) acts as ...first layer and PAN nanofibers incorporated with magnesium aluminate nanoparticles (MA NP) acts as second layer which was placed between polypropylene spun bonded nonwoven (PP SBN). The morphology of the prepared nanocomposite filter was studied by scanning electron microscopy. The performance of the filter was evaluated against i) bacterial filtration efficiency (BFE) with inhibition property ii) PM2.5 aerosol filtration efficiency (AFE) and iii) chemical detoxification efficiency. The developed nanocomposite air filter showed 99% filtration efficiency against bacterial agent & PM2.5 and 95% detoxification against 2-choloro ethyl ethyl sulfide (2-CEES). The result obtained showed that the developed layer by layer nanocomposite filter has the potential application against ABC removal.
Expanded polystyrene (EPS) foam (thermocol waste) is produced at a rate of several million tons annually and poses serious environmental challenges due to its widespread use and lack of ...biodegradability. The present research is to design an effective Malachite Green (MG) dye adsorbent, RBT (Recycled polystyrene (RPS)—Benzophenone-3,3′,4′,4′-Tetracarboxylic dianhydride (BPTCDA)) by the chemical modification of RPS with BPTCDA via two-step reactions (namely the Friedel–Crafts followed by amidation reactions). The adsorbent’s characteristics were studied using the Scanning Electron Microscope (SEM), X-Ray diffraction analysis (XRD), and Fourier-transform infrared spectroscopy (FTIR) techniques. Solution pH, contact duration, initial dye concentration, adsorbent dose, and temperature of the adsorption process were individually optimized. The adsorption is well matched (
R
2
> 0.955) with pseudo second-order kinetics, and Freundlich isotherm was identified as most fitting with research findings. Thermodynamic analysis suggests that the adsorption is spontaneous and endothermic. The probable mechanism behind adsorption was predicted between adsorbent and adsorbate through FT-IR analysis. Finally, MG adsorbed RBT, was converted into 3D printing filaments by the extrusion process. When MG leaching of 3D filaments was evaluated, there was no evidence of MG leaching, which could imply that this approach is an environmentally benign way to remove toxic pollutants as well as reduce landfill polymer waste. Based on the adsorption experiment results, RBT is suitable for the adsorption of MG dye from a water-based medium; also the final product was converted into value-added products.
Graphical Abstract
PDF
