Selén (Se) je esenciálny výživový doplnok pre živočíchov, vrátane človeka, u ktorého sa predpokladá, že znižuje riziko vzniku rakoviny. Hoci podstata tohto javu nie je zatiaľ objasnená, boli navrhnuté viaceré mechanizmy jeho protirakovinného účinku. Tie zahŕňajú ochranu pred oxidačným stresom, stimuláciu opravy DNA a indukciu apoptózy v predrakoviných štádiách. Napriek negatívnym výsledkom poslednej epidemiologickej štúdie „SELECT“, väčšina predchádzajúcich štúdií demonštrovala selénom sprostredkované zníženie výskytu rakovinných ochorení. Navyše poznatky z posledného obdobia naznačujú, že Se má potenciál byť využitý okrem prevencie aj v liečbe rakoviny. Bolo pozorované, že Se buď samotný, alebo v kombinácii s inými liekmi alebo žiarením zvyšuje účinnosť protirakovinnej liečby. V boji s rakovinovými bunkami pôsobí Se skôr ako prooxidant než ako antioxidant, indukujúc apoptózu prostredníctvom oxidačného stresu. Preto sú anorganické formy Se, ktoré majú vysoký redox potenciál, sľubnou alternatívou pre ich perspektívne využitie v nádorovej terapii.
Selenium (Se) is an essential dietary component for all animals, including human beings, that is regarded as a protective agent against cancer. Although the mode of its anticancer action is not yet fully understood, several mechanisms, such as antioxidant protection through selenoenzymes, stimulation of DNA repair, and apoptosis in tumor prestages have all been proposed. Despite the unsupported results of the last ”SELECT“ trial, the cancer-preventing activity of Se has been demonstrated in a majority of epidemiological studies. Moreover, recent studies suggest that Se has a potential to be used not only in cancer prevention but also in cancer treatment, where in combination with other anticancer drugs or radiation it may increase the efficacy of cancer therapy. In combating cancer cells, Se acts as a prooxidant rather than an antioxidant, inducing apoptosis through the generation of oxidative stress. Thus, inorganic Se compounds, having high redox potency, represent a promising option in cancer therapy.
- MeSH
- Anticarcinogenic Agents therapeutic use MeSH
- Apoptosis drug effects MeSH
- Chemoprevention MeSH
- Financing, Organized MeSH
- Humans MeSH
- Neoplasms drug therapy prevention & control MeSH
- Reactive Oxygen Species therapeutic use MeSH
- Selenium pharmacology adverse effects therapeutic use MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Review MeSH
Do dnešní doby byl shromážděn dostatek pozorování a důkazů o esencialitě u nás poměrně opomíjeného stopového prvku selenu. Selen ve formě selenocysteinu vázaného v proteinech a snad i některých nízkomolekulárních sloučeninách hraje důležitou úlohu v ochraně a regulaci řady dějů v lidském organismu. K jeho zatím nejdůležitějším známým funkcím patří antioxidativní ochrana, vliv na imunitní reakce, eliminace vlivu těžkých kovů a regulace působení thyroideálních hormonů tvorbou a deaktivací aktivního hormonu T3. Těmito, ale možná i dalšími ještě neznámými mechanizmy chrání selen organizmus před tzv. -civilizačními nemocemi-, jako jsou kardiovaskulární choroby (včetně infarktu myokardu a mozkové mrtvice), rakovina, zánětlivá onemocnění či neurodegenerativní onemocnění včetně zpomalení stárnutí. Další poznatky ukazují na roli selenu ve vývoji, na vliv na fertilitu mužů a těhotenství žen, na psychiku a náladu. Při dostatečném stavu selenu v organizmu je snížena exprese virů a zpomalen vývoj AIDS u pacientů s HIV. Nejčastěji užívanými indexy stavu selenu (selen v séru a moči) byl sledován stav zásobení selenem u obyvatel ČR. Značná část obyvatel trpí nedostatkem selenu, který sice není tak katastrofální jako v oblastech postižených epidemiologickým výskytem chorob z nedostatku selenu (Keshan disease, Kashin-Beck disease, myxedematózní kretenizmus), nicméně je jedním z nejhlubších v Evropě i tak známé deficitem selenu.
Up to now, a large body of evidence has been collected on essentiality of trace element selenium. Selenium in the form of selenocysteine incorporated into proteins and possibly also as some low-molecular compounds plays important roles in various protective and regulatory biochemical pathways and physiological functions of the organism. Antioxidative effect, influence upon immunity, detoxification of heavy metals, and regulation of the thyroid hormone metabolism and functions by activation and deactivation of thyromimetically active hormone T3 are the best known selenium functions. By these and possibly even others not yet known mechanisms prevents selenium many so called -civilization diseases- like cardiovascular diseases (including myocardial infarct and stroke), cancer, inflammatory diseases, and neurodegenerative diseases including slowing the ageing process. Further evidence points its role in development, male fertility and female pregnancy, or psychics and mood. Viral expression is reduced and the progression of AIDS in HIV infected patients is delayed under the condition of sufficient selenium. According the most often used indexes of Se status (blood serum and urine), inhabitants of the Czech Republic suffer from serious Se deficiency, which is not so profound as in the countries with epidemiological diseases occurrence (Keshan disease, Kashin-Beck disease, Myxedematous cretinism) but is worse than in most other European countries, which are known to be selenium-deficient.
- MeSH
- Antioxidants metabolism MeSH
- Thyroid Hormones metabolism MeSH
- Immunity MeSH
- Humans MeSH
- Selenium analysis blood metabolism MeSH
- Selenium Compounds metabolism deficiency MeSH
- Health MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
V první části článku (Interní medicína pro praxi 2003; 6: 295-300) byly v krátkosti shrnuty biochemické reakce zpracování selenu v organizmu a jeho včlenění do selenoproteinů na základě genetické informace, z čehož vyplývá klasifikace selenocysteinu jako 21. aminokyseliny. Byly popsány dosud známé selenoproteiny s uvedením jejich funkce (je-li známa) a byl popsán vliv selenu, resp. jeho nedostatku na některé fyziologické a biochemické pochody, ovlivňující činnost a zdravotní stav organismu. Na základě funkcí selenoproteinů byl nastíněn možný vliv nedostatku selenu na kardiovaskulární choroby, reprodukci, virulenci a patogenicitu některých virů a rovněž vliv selenu na imunitní odezvu organizmu. V následujících odstavcích bude pokračovat popis efektů sloučenin selenu v organizmu uvedením jejich antikancerogenních účinků na různých úrovních (zde se autor bude odvolávat i na některé mechanizmy vyložené v 1. části), životně důležitou katalytickou činností dejodáz při tvorbě a degradaci thyreoidálních hormonů a budou shrnuty dosavadní víceméně empirické znalosti o působení selenu na psychiku. Možnosti určování stavu selenu v organizmu a stav selenu u populace ČR budou námětem posledního tematického okruhu spolu s uvedením možností intervence u celé populace i jednotlivců.
In the first part of the article (Interní medicína pro praxi 2003; 6: 295-300) there were shortly summarised biochemical pathways of selenium in the organism and incorporation of Se-cystein into selenoprotein as 21. aminoacid on the grounds of genetic information. The table of the known selenoproteins was included with the information about up to now known functions of selenium compounds. Influences of selenium and/or its deficiency on some physiological and biochemical pathways with the effect upon health status and function of organism were also mentioned, especially effect upon cardiovascular diseases, reproduction, pathogenicity of some viruses, and effect of selenium upon immune response. In this second part, carcinostatic effects of selenium compounds, catalytic activity of deiodinases in the metabolism and regulation of thyroid hormones, as well as less or more empirical knowledge on effect of selenium upon psychics will be discussed. Possibilities of the detection of selenium status indexes and selenium status of the population in the Czech Republic as well will be the topic of the last chapters of the article, together with the summary of intervention possibilities both on the whole population scale and for individuals.
The trace element selenium (Se) is a crucial element for many living organisms, including soil microorganisms, plants and animals, including humans. Generally, in Nature Se is taken up in the living cells of microorganisms, plants, animals and humans in several inorganic forms such as selenate, selenite, elemental Se and selenide. These forms are converted to organic forms by biological process, mostly as the two selenoamino acids selenocysteine (SeCys) and selenomethionine (SeMet). The biological systems of plants, animals and humans can fix these amino acids into Se-containing proteins by a modest replacement of methionine with SeMet. While the form SeCys is usually present in the active site of enzymes, which is essential for catalytic activity. Within human cells, organic forms of Se are significant for the accurate functioning of the immune and reproductive systems, the thyroid and the brain, and to enzyme activity within cells. Humans ingest Se through plant and animal foods rich in the element. The concentration of Se in foodstuffs depends on the presence of available forms of Se in soils and its uptake and accumulation by plants and herbivorous animals. Therefore, improving the availability of Se to plants is, therefore, a potential pathway to overcoming human Se deficiencies. Among these prospective pathways, the Se-biofortification of plants has already been established as a pioneering approach for producing Se-enriched agricultural products. To achieve this desirable aim of Se-biofortification, molecular breeding and genetic engineering in combination with novel agronomic and edaphic management approaches should be combined. This current review summarizes the roles, responses, prospects and mechanisms of Se in human nutrition. It also elaborates how biofortification is a plausible approach to resolving Se-deficiency in humans and other animals.
- MeSH
- Antioxidants chemistry metabolism MeSH
- Biofortification * MeSH
- Selenic Acid chemistry metabolism MeSH
- Humans MeSH
- Soil chemistry MeSH
- Plants metabolism MeSH
- Selenium chemistry metabolism MeSH
- Selenocysteine chemistry metabolism MeSH
- Selenomethionine chemistry metabolism MeSH
- Selenoproteins biosynthesis metabolism MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
- MeSH
- Acquired Immunodeficiency Syndrome MeSH
- Apoptosis MeSH
- Neoplasms prevention & control MeSH
- Oxidative Stress MeSH
- Selenium metabolism MeSH
- Publication type
- Congress MeSH
Drought poses a serious threat to oilseed crops by lowering yield and crop failures under prolonged spells. A multi-year field investigation was conducted to enhance the drought tolerance in four genotypes of Camelina and canola by selenium (Se) application. The principal aim of the research was to optimize the crop yield by eliciting the physio-biochemical attributes by alleviating the adverse effects of drought stress. Both crops were cultivated under control (normal irrigation) and drought stress (skipping irrigation at stages i.e., vegetative and reproductive) conditions. Four different treatments of Se viz., seed priming with Se (75 μM), foliar application of Se (7.06 μM), foliar application of Se + Seed priming with Se (7.06 μM and 75 μM, respectively) and control (without Se), were implemented at the vegetative and reproductive stages of both crops. Sodium selenite (Na2SeO3), an inorganic compound was used as Se sources for both seed priming and foliar application. Data regarding physiochemical, antioxidants, and yield components were recorded as response variables at crop maturity. Results indicated that WP, OP, TP, proline, TSS, TFAA, TPr, TS, total chlorophyll contents, osmoprotectant (GB, anthocyanin, TPC, and flavonoids), antioxidants (APX, SOD, POD, and CAT), and yield components (number of branches per plant, thousand seed weight, seed, and biological yields were significantly improved by foliar Se + priming Se in both crops under drought stress. Moreover, this treatment was also helpful in boosting yield attributes under irrigated (non-stress) conditions. Camelina genotypes responded better to Se application as seed priming and foliar spray than canola for both years. It has concluded that Se application (either foliar or priming) can potentially alleviate adverse effects of drought stress in camelina and canola by eliciting various physio-biochemicals attributes under drought stress. Furthermore, Se application was also helpful for crop health under irrigated condition.
- MeSH
- Antioxidants analysis MeSH
- Brassica napus drug effects growth & development physiology MeSH
- Brassicaceae drug effects growth & development physiology MeSH
- Droughts * MeSH
- Rapeseed Oil isolation & purification MeSH
- Plant Oils isolation & purification MeSH
- Osmoregulation MeSH
- Plant Proteins analysis MeSH
- Selenium administration & dosage MeSH
- Crops, Agricultural drug effects growth & development physiology MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Pakistan MeSH
Dietary selenium (Se) intake is essential for synthesizing selenoproteins that are important in countering oxidative and inflammatory processes linked to colorectal carcinogenesis. However, there is limited knowledge on the selenoprotein expression in colorectal adenoma (CRA) and colorectal cancer (CRC) patients, or the interaction with Se status levels. We studied the expression of seventeen Se pathway genes (including fifteen of the twenty-five human selenoproteins) in RNA extracted from disease-normal colorectal tissue pairs, in the discovery phase of sixty-two CRA/CRC patients from Ireland and a validation cohort of a hundred and five CRC patients from the Czech Republic. Differences in transcript levels between the disease and paired control mucosa were assessed by the Mann-Whitney U-test. GPX2 and TXNRD3 showed a higher expression and GPX3, SELENOP, SELENOS, and SEPHS2 exhibited a lower expression in the disease tissue from adenomas and both cancer groups (p-values from 0.023 to <0.001). In the Czech cohort, up-regulation of GPX1, SELENOH, and SOD2 and down-regulation of SELENBP1, SELENON, and SELENOK (p-values 0.036 to <0.001) was also observed. We further examined the correlation of gene expression with serum Se status (assessed by Se and selenoprotein P, SELENOP) in the Irish patients. While there were no significant correlations with both Se status markers, SELENOF, SELENOK, and TXNRD1 tumor tissue expression positively correlated with Se, while TXNRD2 and TXNRD3 negatively correlated with SELENOP. In an analysis restricted to the larger Czech CRC patient cohort, Cox regression showed no major association of transcript levels with patient survival, except for an association of higher SELENOF gene expression with both a lower disease-free and overall survival. Several selenoproteins were differentially expressed in the disease tissue compared to the normal tissue of both CRA and CRC patients. Altered selenoprotein expression may serve as a marker of functional Se status and colorectal adenoma to cancer progression.
- MeSH
- Adenoma blood genetics MeSH
- Genetic Markers MeSH
- Glutathione Peroxidase genetics metabolism MeSH
- Cohort Studies MeSH
- Colorectal Neoplasms blood genetics MeSH
- Middle Aged MeSH
- Humans MeSH
- Proportional Hazards Models MeSH
- Gene Expression Regulation MeSH
- Selenium blood MeSH
- Selenoprotein P genetics metabolism MeSH
- Selenoproteins genetics metabolism MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Thioredoxin-Disulfide Reductase genetics metabolism MeSH
- Thioredoxin Reductase 1 genetics metabolism MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Czech Republic MeSH
- Ireland MeSH
The mechanisms of sodium selenite-induced cell death in cervical carcinoma cells were studied during 24 h of exposure in the HeLa Hep-2 cell line. Selenite at the employed concentrations of 5 and 50 micromol/L produced time- and dose-dependent suppression of DNA synthesis and induced DNA damage which resulted in phosphorylation of histone H2A.X. These effects were influenced by pretreatment of cells with the SOD/catalase mimetic MnTMPyP or glutathione-depleting buthionine sulfoximine, suggesting the significant role of selenite-generated oxidative stress. Following the DNA damage, selenite activated p53-dependent pathway as evidenced by the appearance of phosphorylated p53 and accumulation of p21 in the treated cells. Concomitantly, selenite activated p38 pathway but its effect on JNK was very weak. p53- and p38-dependent signaling led to the accumulation of Bax protein, which was preventable by specific inhibitors of p38 (SB 203580) and p53 (Pifithrin-alpha). Mitochondria in selenite-treated cells changed their dynamics (shape and localization) and released AIF and Smac/Diablo, which initiated caspase-independent apoptosis as confirmed by the caspase-3 activity assay and the low effect of caspase inhibitors z-DEVD-fmk and z-VAD-fmk on cell death. We conclude that selenite induces caspase-independent apoptosis in cervical carcinoma cells mostly by oxidative stress-mediated activation of p53 and p38 pathways, but other selenite-mediated effects, in particular mitochondria-specific ones, are also involved.
- MeSH
- Enzyme Activation drug effects MeSH
- Bromodeoxyuridine pharmacology metabolism MeSH
- Cell Death drug effects MeSH
- DNA, Neoplasm biosynthesis MeSH
- Apoptosis Inducing Factor metabolism MeSH
- Financing, Organized MeSH
- Glutathione metabolism MeSH
- HeLa Cells MeSH
- Cyclin-Dependent Kinase Inhibitor p21 metabolism MeSH
- Intracellular Signaling Peptides and Proteins metabolism MeSH
- JNK Mitogen-Activated Protein Kinases metabolism MeSH
- Caspase 3 metabolism MeSH
- Humans MeSH
- Metalloporphyrins MeSH
- Mitochondrial Proteins metabolism MeSH
- p38 Mitogen-Activated Protein Kinases metabolism MeSH
- Tumor Suppressor Protein p53 metabolism MeSH
- Uterine Cervical Neoplasms enzymology pathology MeSH
- Oxidative Stress drug effects MeSH
- DNA Damage MeSH
- Selenium pharmacology MeSH
- Organelle Shape drug effects MeSH
- Check Tag
- Humans MeSH
- Female MeSH
Epidemiological data indicate that selenium status is inversely connected with cancer risk. Animal and human studies have demonstrated that most inorganic and organic forms of selenium compounds have an anticancer action. This work investigated the impact of organic selenium on the multiple signalling pathways involved in the inhibition of the viability of prostate cancer cells. Prostate adenocarcinoma cells (PC-3) were incubated with seleno-l-methionine (SeMet) at four concentrations and cell viability and programmed cell death were determined by the WST-1, BrdU assays and Tali image based cytometer. The expression of chosen cell-cycle regulatory genes was determined by real-time RT-PCR analysis and confirmed at the protein level. SeMet treatment of PC-3 cells resulted in an inhibition of cell proliferation in a dose- and time-dependent manner. The inhibition of proliferation correlated with the up-regulation of gene expression and the protein levels of CCNG1, CHEK1, CDKN1C and GADD45A, whereas SeMet down-regulated the expression of CCNA1 and CDK6 genes. Therefore SeMet inhibits the proliferative activity of prostate cancer cells by a direct influence on the expression of genes involved in the regulation of cell cycle progression.
- MeSH
- Adenocarcinoma drug therapy genetics MeSH
- Apoptosis genetics drug effects MeSH
- Time Factors MeSH
- Genes, cdc drug effects MeSH
- Gene Expression drug effects MeSH
- Cell Line, Tumor * drug effects MeSH
- Prostatic Neoplasms * drug therapy genetics MeSH
- Reverse Transcriptase Polymerase Chain Reaction MeSH
- Cell Proliferation drug effects MeSH
- Cell Cycle Proteins genetics drug effects MeSH
- Gene Expression Regulation, Neoplastic MeSH
- Selenium MeSH
- Selenomethionine * administration & dosage MeSH
- Statistics as Topic MeSH
- In Vitro Techniques MeSH
- Cell Survival * drug effects MeSH
- Dose-Response Relationship, Drug MeSH
- Blotting, Western MeSH
- Publication type
- Evaluation Study MeSH
- Research Support, Non-U.S. Gov't MeSH
Se-Enriched defatted rapeseed (Se-DRS), a by-product of rapeseed oil production, is high in Se. This study aimed to detect possible changes in Se-metabolism after Se-DRS consumption and to assess its suitability as a Se supplement in monogaster feed. In this experiment, rats were fed three types of diets differing in Se-form: soybean meal, Se-salt and Se-DRS. Potential differences in Se-metabolism were evaluated based on the total Se concentrations along with non-protein Se speciation patterns in the urine and blood serum of the rats. The total Se concentrations were determined using inductively coupled plasma-mass spectrometry (ICP-MS). Se compounds in the samples were identified through high-performance liquid chromatography/ICP-MS. The total Se excretion rate was dose-dependent, and excess of dietary Se was eliminated in the form of Se-sugar 1, regardless of the administered Se-form. The excretion dynamics of dietary selenomethionine (soybean meal) and methylselenocysteine (Se-DRS) were different to that of the mineral Se (Se-salt). The proportions of Se species in the urine were significantly influenced by the Se source. A specific metabolic pathway, resulting in urinary excretion of Se-sugar 2, was observed in animals fed Se-DRS. Neither the total Se concentrations nor the serum Se speciation patterns differed between the animals fed the conventional diet and those fed the Se-DRS-enriched diet. Based on these results, Se-DRS can be considered a suitable Se supplement for monogaster nutrition in Se-deficient regions.
- MeSH
- Brassica rapa chemistry MeSH
- Food, Fortified * MeSH
- Animal Feed MeSH
- Rats MeSH
- Rats, Wistar MeSH
- Dietary Supplements * MeSH
- Eating MeSH
- Selenium metabolism urine MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
