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Pathology Oncology Research : POR Oct 2020The unique character of selenium compounds, including sodium selenite and Se-methylselenocysteine (MSC), is that they exert cytotoxic effects on neoplastic cells,...
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 values were determined by performing SRB proliferation assays. The results revealed much lower IC 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. 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.
Topics: Anticarcinogenic Agents; Apoptosis; Biomarkers, Tumor; Carcinoma, Hepatocellular; Cell Proliferation; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Liver Neoplasms; MicroRNAs; Selenocysteine; Sodium Selenite; Trace Elements; Tumor Cells, Cultured
PubMed: 32656599
DOI: 10.1007/s12253-020-00870-8 -
Cancers Jun 2021Sodium selenite acts by depleting enzymes that protect against cellular oxidative stress. To determine its effect alone or in combination with gemcitabine (GMZ) in...
Sodium selenite acts by depleting enzymes that protect against cellular oxidative stress. To determine its effect alone or in combination with gemcitabine (GMZ) in pancreatic cancer, we used PANC-1 and Pan02 cell lines and C57BL mice bearing a Pan02-generated tumor. Our results demonstrated a significant inhibition of pancreatic cancer cell viability with the use of sodium selenite alone and a synergistic effect when associated with GMZ. The molecular mechanisms of the antitumor effect of sodium selenite alone involved apoptosis-inducing factor (AIF) and the expression of phospho-p38 in the combined therapy. In addition, sodium selenite alone and in association with GMZ significantly decreased the migration capacity and colony-forming ability, reduced tumor activity in multicellular tumor spheroids (MTS) and decreased sphere formation of cancer stem cells. In vivo studies demonstrated that combined therapy not only inhibited tumor growth (65%) compared to the untreated group but also relative to sodium selenite or GMZ used as monotherapy (up to 40%), increasing mice survival. These results were supported by the analysis of C57BL/6 albino mice bearing a Pan02-generated tumor, using the IVIS system. In conclusion, our results showed that sodium selenite is a potential agent for the improvement in the treatment of pancreatic cancer and should be considered for future human clinical trials.
PubMed: 34201986
DOI: 10.3390/cancers13133169 -
Journal of Dairy Science Aug 2020Undesirable interactions between trace mineral elements and ruminal contents may occur during digestion when mineral salts are supplemented. Antimicrobial effects of...
Undesirable interactions between trace mineral elements and ruminal contents may occur during digestion when mineral salts are supplemented. Antimicrobial effects of copper sulfate (CuSO) may affect ruminal digestibility of nutrients when fed as a source of copper (Cu), while sodium selenite (NaSeO) may be reduced in the rumen to less available forms of selenium (Se). Our objective was to evaluate if protection of CuSO and NaSeO by lipid-microencapsulation would induce changes on ruminal microbial fermentation. We used 8 fermentors in a dual-flow continuous-culture system in a 4 × 4 duplicated Latin square with a 2 × 2 factorial arrangement of treatments. Factors were CuSO protection (unprotected and protected by lipid-microencapsulation) and NaSeO protection (unprotected and protected by lipid-microencapsulation). Treatments consisted of supplementation with 15 mg/kg of Cu and 0.3 mg/kg of Se from either unprotected or protected (lipid-microencapsulated) sources, as follows: (1) Control (unprotected CuSO + unprotected NaSeO); (2) Cu-P (protected CuSO + unprotected NaSeO); (3) Se-P (unprotected CuSO + protected NaSeO); (4) (Cu+Se)-P (protected CuSO + protected NaSeO). All diets had the same nutrient composition and fermentors were fed 106 g of dry matter/d. Each experimental period was 10 d (7 d of adaptation and 3 d for sample collections). Daily pooled samples of effluents were analyzed for pH, NH-N, nutrient digestibility, and flows (g/d) of total N, NH-N, nonammonia N (NAN), bacterial N, dietary N, and bacterial efficiency. Kinetics of volatile fatty acids was analyzed in samples collected daily at 0, 1, 2, 4, 6, and 8 h after feeding. Main effects of Cu protection, Se protection, and their interaction were tested for all response variables. Kinetics data were analyzed as repeated measures. Protection of Cu decreased acetate molar proportion, increased butyrate proportion, and tended to decrease acetate:propionate ratio in samples of kinetics, but did not modify nutrient digestibility. Protection of Se tended to decrease NH-N concentration, NH-N flow, and CP digestibility; and to increase flows of nonammonia N and dietary N. Our results indicate that protection of CuSO may increase butyrate concentration at expenses of acetate, while protection of NaSeO tended to reduce ruminal degradation of N. Further research is needed to determine the effects of lipid-microencapsulation on intestinal absorption, tissue distribution of Cu and Se, and animal performance.
Topics: Animal Feed; Animals; Bacteria; Bioreactors; Cattle; Copper Sulfate; Culture Techniques; Diet; Dietary Supplements; Digestion; Drug Compounding; Fatty Acids, Volatile; Female; Fermentation; Lipids; Nutrients; Rumen; Sodium Selenite; Trace Elements
PubMed: 32505403
DOI: 10.3168/jds.2019-17913 -
International Journal of Molecular... Sep 2021Glioblastoma (GBM) is the most aggressive malignant glioma, with a very poor prognosis; as such, efforts to explore new treatments and GBM's etiology are a priority. We...
Glioblastoma (GBM) is the most aggressive malignant glioma, with a very poor prognosis; as such, efforts to explore new treatments and GBM's etiology are a priority. We previously described human GBM cells (R2J-GS) as exhibiting the properties of cancer stem cells (growing in serum-free medium and proliferating into nude mice when orthotopically grafted). Sodium selenite (SS)-an in vitro attractive agent for cancer therapy against GBM-was evaluated in R2J-GS cells. To go further, we launched a preclinical study: SS was given orally, in an escalation-dose study (2.25 to 10.125 mg/kg/day, 5 days on, 2 days off, and 5 days on), to evaluate (1) the absorption of selenium in plasma and organs (brain, kidney, liver, and lung) and (2) the SS toxicity. A 6.75 mg/kg SS dose was chosen to perform a tumor regression assay, followed by MRI, in R2J-GS cells orthotopically implanted in nude mice, as this dose was nontoxic and increased brain selenium concentration. A group receiving TMZ (5 mg/kg) was led in parallel. Although not reaching statistical significance, the group of mice treated with SS showed a slower tumor growth vs. the control group ( = 0.08). No difference was observed between the TMZ and control groups. We provide new insights of the mechanisms of SS and its possible use in chemotherapy.
Topics: Animals; Apoptosis; Brain Neoplasms; Cell Cycle Checkpoints; Cell Line, Tumor; Cell Proliferation; Corpus Striatum; Glioblastoma; Humans; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplastic Stem Cells; Selenium; Sodium Selenite; Temozolomide; Trace Elements; Treatment Outcome; Tumor Burden; Xenograft Model Antitumor Assays
PubMed: 34638987
DOI: 10.3390/ijms221910646 -
Molecular Medicine Reports May 2018The present study aimed to examine the effects of sodium selenite on the SW982 human synovial sarcoma cell line in relation to cell viability, apoptosis and autophagy....
The present study aimed to examine the effects of sodium selenite on the SW982 human synovial sarcoma cell line in relation to cell viability, apoptosis and autophagy. The results indicated that sodium selenite reduced cell viability and induced apoptosis by activating caspase‑3 and members of the poly (ADP‑ribose) polymerase and Bcl‑2 protein families in SW982 cells. Furthermore, autophagy was also suppressed by sodium selenite treatment in SW982 cells, and apoptosis was upregulated in cells co‑treated with sodium selenite and the autophagy inhibitor 3‑methyladenine. By contrast, apoptosis was downregulated when sodium selenite was combined with rapamycin, an inducer of autophagy. The results indicated that autophagy may protect cells from the cytotoxicity of sodium selenite. The present study results demonstrated that sodium selenite induced apoptosis and inhibited autophagy and autophagy‑protected cells from death by antagonizing sodium selenite‑induced apoptosis in SW982 cells in vitro.
Topics: Apoptosis; Autophagy; Caspase 3; Cell Line, Tumor; Humans; Poly(ADP-ribose) Polymerases; Proto-Oncogene Proteins c-bcl-2; Sarcoma, Synovial; Sodium Selenite
PubMed: 29512717
DOI: 10.3892/mmr.2018.8679 -
Journal of Hematology & Oncology Jan 2013Previous studies demonstrated that selenite induced cancer-cell apoptosis through multiple mechanisms; however, effects of selenite on microtubules in leukemic cells...
BACKGROUND
Previous studies demonstrated that selenite induced cancer-cell apoptosis through multiple mechanisms; however, effects of selenite on microtubules in leukemic cells have not been demonstrated.
METHODS
The toxic effect of selenite on leukemic HL60 cells was performed with cell counting kit 8. Selenite effects on cell cycle distribution and apoptosis induction were determined by flow cytometry. The contents of cyclin B1, Mcl-1, AIF, cytochrome C, insoluble and soluble tubulins were detected with western blotting. Microtubules were visualized with indirect immunofluorescence microscopy. The interaction between CDK1 and Mcl-1 was assessed with immunoprecipitation. Decreasing Mcl-1 and cyclin B1 expression were carried out through siRNA interference. The alterations of Mcl-1 and cyclin B1 in animal model were detected with either immunohistochemical staining or western blotting. In situ detection of apoptotic ratio was performed with TUNEL assay.
RESULTS
Our current results showed that selenite inhibited the growth of HL60 cells and induced mitochondrial-related apoptosis. Furthermore, we found that microtubule assembly in HL60 cells was altered, those cells were arrested at G2/M phase, and Cyclin B1 was up-regulated and interacted with CDK1, which led to down-regulation of the anti-apoptotic protein Mcl-1. Finally, in vivo experiments confirmed the in vitro microtubule disruption effect and alterations in Cyclin B1 and Mcl-1 levels by selenite.
CONCLUSIONS
Taken together, the results from our study indicate that microtubules are novel targets of selenite in leukemic HL60 cells.
Topics: Animals; Apoptosis; Blotting, Western; Calcium-Binding Proteins; Cell Division; Cyclin B1; Cytochromes c; DNA-Binding Proteins; Female; Fluorescent Antibody Technique; G2 Phase; HL-60 Cells; Humans; Immunoenzyme Techniques; Immunoprecipitation; In Situ Nick-End Labeling; In Vitro Techniques; Mice; Microfilament Proteins; Microtubules; Myeloid Cell Leukemia Sequence 1 Protein; Proto-Oncogene Proteins c-bcl-2; RNA, Small Interfering; Sodium Selenite; Xenograft Model Antitumor Assays
PubMed: 23327530
DOI: 10.1186/1756-8722-6-7 -
Free Radical Biology & Medicine Nov 2022Keshan disease is an endemic fatal dilated cardiomyopathy that can cause heart enlargement, heart failure, and cardiogenic death. Selenium deficiency is considered to be...
Keshan disease is an endemic fatal dilated cardiomyopathy that can cause heart enlargement, heart failure, and cardiogenic death. Selenium deficiency is considered to be the main cause of Keshan disease. However, the molecular mechanism underlying Keshan disease remains unclear. Our whole-exome sequencing from 68 patients with Keshan disease and 100 controls found 199 candidate genes by gene-level burden tests. Interestingly, using multiomics data, the selenium-related gene ALAD (δ-aminolevulinic acid dehydratase) was the only candidate causative gene identified by three different analysis approaches. Based on single-cell transcriptome data, ALAD was highly expressed in cardiomyocytes and double mutations of human ALAD dramatically reduced its enzyme activity in vitro compared to negative control. Functional analysis of ALAD inhibition in mice resulted in a Keshan phenotype with left ventricular enlargement and cardiac dysfunction, whereas administration of sodium selenite markedly reversed the changes caused by ALAD inhibition. In addition, sodium selenite reversed Keshan phenotypes by affecting energy metabolism and mitochondrial function in mice as shown by the transcriptomic and proteomic data and the ultrastructure of cardiac myocytes. Our findings are the first to demonstrate that the selenium-related gene ALAD is essential for cardiac function by maintaining normal mitochondrial activity, providing strong molecular evidence supporting the hypothesis of selenium deficiency in Keshan disease. These results identified ALAD as a novel target for therapeutic intervention in Keshan disease and Keshan disease-related dilated cardiomyopathy.
Topics: Humans; Mice; Animals; Selenium; Cardiomyopathy, Dilated; Sodium Selenite; Proteomics; Malnutrition
PubMed: 36395956
DOI: 10.1016/j.freeradbiomed.2022.11.014 -
Journal of Nanobiotechnology Mar 2022Selenium nanoparticles (SeNPs) have attracted considerable attention globally due to their significant potential for alleviating abiotic stresses in plants. Accordingly,...
Comparative efficacy of bio-selenium nanoparticles and sodium selenite on morpho-physiochemical attributes under normal and salt stress conditions, besides selenium detoxification pathways in Brassica napus L.
Selenium nanoparticles (SeNPs) have attracted considerable attention globally due to their significant potential for alleviating abiotic stresses in plants. Accordingly, further research has been conducted to develop nanoparticles using chemical ways. However, our knowledge about the potential benefit or phytotoxicity of bioSeNPs in rapeseed is still unclear. Herein, we investigated the effect of bioSeNPs on growth and physiochemical attributes, and selenium detoxification pathways compared to sodium selenite (Se (IV)) during the early seedling stage under normal and salt stress conditions. Our findings showed that the range between optimal and toxic levels of bioSeNPs was wider than Se (IV), which increased the plant's ability to reduce salinity-induced oxidative stress. BioSeNPs improved the phenotypic characteristics of rapeseed seedlings without the sign of toxicity, markedly elevated germination, growth, photosynthetic efficiency and osmolyte accumulation versus Se (IV) under normal and salt stress conditions. In addition to modulation of Na and K uptake, bioSeNPs minimized the ROS level and MDA content by activating the antioxidant enzymes engaged in ROS detoxification by regulating these enzyme-related genes expression patterns. Importantly, the main effect of bioSeNPs and Se (IV) on plant growth appeared to be correlated with the change in the expression levels of Se-related genes. Our qRT-PCR results revealed that the genes involved in Se detoxification in root tissue were upregulated upon Se (IV) treated seedlings compared to NPs, indicating that bioSeNPs have a slightly toxic effect under higher concentrations. Furthermore, bioSeNPs might improve lateral root production by increasing the expression level of LBD16. Taken together, transamination and selenation were more functional methods of Se detoxification and proposed different degradation pathways that synthesized malformed or deformed selenoproteins, which provided essential mechanisms to increase Se tolerance at higher concentrations in rapeseed seedlings. Current findings could add more knowledge regarding the mechanisms underlying bioSeNPs induced plant growth.
Topics: Brassica napus; Nanoparticles; Salt Stress; Selenium; Sodium Selenite
PubMed: 35351148
DOI: 10.1186/s12951-022-01370-4 -
Journal of Medical Virology Apr 2016Hepatitis B virus (HBV) infection is one of the most serious and prevalent health problems worldwide. Current anti-HBV medications have a number of drawbacks, such as...
Hepatitis B virus (HBV) infection is one of the most serious and prevalent health problems worldwide. Current anti-HBV medications have a number of drawbacks, such as adverse effects and drug resistance; thus, novel potential anti-HBV reagents are needed. Selenium (Se) has been shown to be involved in both human immunodeficiency virus and hepatitis C virus infections, but its role in HBV infection remains unclear. To address this, sodium selenite (Na2SeO3 ) was applied to three HBV cell models: HepG2.2.15 cells, and HuH-7 cells transfected with either 1.1 or 1.3× HBV plasmids. Cytotoxicity of Na2SeO3 was examined by Cell Counting Kit-8. Levels of viral antigen expression, transcripts, and encapsidated viral DNA were measured by enzyme-linked immunosorbent assay, northern blot, and Southern blot, respectively. There was no obvious cytotoxicity in either HepG2.2.15 or HuH-7 cells with <2.5 µM Na2SeO3 . Below this concentration, Na2SeO3 suppressed HBsAg and HBeAg production, HBV transcript level, and amount of genomic DNA in all three tested models, and suppression level was enhanced in line with increases in Na2 SeO3 concentration or treatment time. Moreover, the inhibitory effect of Na2SeO3 on HBV replication can be further enhanced by combined treatment with lamivudine, entecavir, or adefovir. Thus, the present study clearly proves that Na2SeO3 suppresses HBV protein expression, transcription, and genome replication in hepatoma cell models in a dose- and time-dependent manner.
Topics: Antigens, Viral; Antiviral Agents; Blotting, Northern; Blotting, Southern; Cell Line, Tumor; Cell Survival; DNA, Viral; Drug Interactions; Enzyme-Linked Immunosorbent Assay; Hepatitis B virus; Hepatocytes; Humans; RNA, Viral; Sodium Selenite; Transcription, Genetic; Virus Replication
PubMed: 26331371
DOI: 10.1002/jmv.24366 -
International Journal of Molecular... Feb 2022The review presents the latest data on the role of selenium-containing agents in the regulation of diseases of the immune system. We mainly considered the contributions... (Review)
Review
The review presents the latest data on the role of selenium-containing agents in the regulation of diseases of the immune system. We mainly considered the contributions of selenium-containing compounds such as sodium selenite, methylseleninic acid, selenomethionine, and methylselenocysteine, as well as selenoproteins and selenium nanoparticles in the regulation of defense mechanisms against various viral infections, including coronavirus infection (COVID-19). A complete description of the available data for each of the above selenium compounds and the mechanisms underlying the regulation of immune processes with the active participation of these selenium agents, as well as their therapeutic and pharmacological potential, is presented. The main purpose of this review is to systematize the available information, supplemented by data obtained in our laboratory, on the important role of selenium compounds in all of these processes. In addition, the presented information makes it possible to understand the key differences in the mechanisms of action of these compounds, depending on their chemical and physical properties, which is important for obtaining a holistic picture and prospects for creating drugs based on them.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Antiviral Agents; Humans; Immune System; Immunomodulating Agents; Organoselenium Compounds; Selenium Compounds; Selenocysteine; Selenomethionine; Sodium Selenite; COVID-19 Drug Treatment
PubMed: 35216476
DOI: 10.3390/ijms23042360