THE MAIN CYTOTOXIC EFFECTS OF METHYLSELENINIC ACID ON VARIOUS CANCER CELLS

Studies of recent decades have repeatedly demonstrated the cytotoxic effect of selenium-containing compounds on cancer cells of various origins. Particular attention in these studies is paid to methylseleninic acid, a widespread selenium-containing compound of organic nature, for several reasons: it has a selective cytotoxic effect on cancer cells, it is cytotoxic in small doses, it is able to generate methylselenol, excluding the action of the enzyme β-lyase. All these qualities make methylseleninic acid an attractive substrate for the production of anticancer drugs on its basis with a well-pronounced selective effect. However, the studies available to date indicate that there is no strictly specific molecular mechanism of its cytotoxic effect in relation to different cancer cell lines and cancer models. This review contains generalized information on the dose- and time-dependent regulation of the toxic effect of methylseleninic acid on the proliferative properties of a number of cancer cell lines. In addition, special attention in this review is paid to the influence of this selenium-containing compound on the regulation of endoplasmic reticulum stress and on the expression of seven selenoproteins, which are localized in the endoplasmic reticulum.     

Role of Selenium in Viral Infections with a Major Focus on SARS-CoV-2

Viral infections have afflicted human health and despite great advancements in scientific knowledge and technologies, continue to affect our society today. The current coronavirus (COVID-19) pandemic has put a spotlight on the need to review the evidence on the impact of nutritional strategies to maintain a healthy immune system, particularly in instances where there are limited therapeutic treatments. Selenium, an essential trace element in humans, has a long history of lowering the occurrence and severity of viral infections. Much of the benefits derived from selenium are due to its incorporation into selenocysteine, an important component of proteins known as selenoproteins. Viral infections are associated with an increase in reactive oxygen species and may result in oxidative stress. Studies suggest that selenium deficiency alters immune response and viral infection by increasing oxidative stress and the rate of mutations in the viral genome, leading to an increase in pathogenicity and damage to the host. This review examines viral infections, including the novel SARS-CoV-2, in the context of selenium, in order to inform potential nutritional strategies to maintain a healthy immune system.     

Size-Dependent Cytoprotective Effects of Selenium Nanoparticles during Oxygen-Glucose Deprivation in Brain Cortical Cells

It is known that selenium nanoparticles (SeNPs) obtained on their basis have a pleiotropic effect, inducing the process of apoptosis in tumor cells, on the one hand, and protecting healthy tissue cells from death under stress, on the other hand. It has been established that SeNPs protect brain cells from ischemia/reoxygenation through activation of the Ca²⁺ signaling system of astrocytes and reactive astrogliosis. At the same time, for a number of particles, the limitations of their use, associated with their size, are shown. The use of nanoparticles with a diameter of less than 10 nm leads to their short life-time in the bloodstream and rapid removal by the liver. Nanoparticles larger than 200 nm activate the complement system and are also quickly removed from the blood. The effects of different-sized SeNPs on brain cells have hardly been studied. Using the laser ablation method, we obtained SeNPs of various diameters: 50 nm, 100 nm, and 400 nm. Using fluorescence microscopy, vitality tests, PCR analysis, and immunocytochemistry, it was shown that all three types of the different-sized SeNPs have a cytoprotective effect on brain cortex cells under conditions of oxygen-glucose deprivation (OGD) and reoxygenation (R), suppressing the processes of necrotic death and inhibiting different efficiency processes of apoptosis. All of the studied SeNPs activate the Ca²⁺ signaling system of astrocytes, while simultaneously inducing different types of Ca²⁺ signals. SeNPs sized at 50 nm- induce Ca²⁺ responses of astrocytes in the form of a gradual irreversible increase in the concentration of cytosolic Ca²⁺ ([Ca²⁺]_i), 100 nm-sized SeNPs induce stable Ca²⁺ oscillations without increasing the base level of [Ca²⁺]_i, and 400 nm-sized SeNPs cause mixed patterns of Ca²⁺ signals. Such differences in the level of astrocyte Ca²⁺ signaling can explain the different cytoprotective efficacy of SeNPs, which is expressed in the expression of protective proteins and the activation of reactive astrogliosis. In terms of the cytoprotective efficiency under OGD/R conditions, different-sized SeNPs can be arranged in descending order: 100 nm-sized > 400 nm-sized > 50 nm-sized.     

Increased intakes of selenium‐enriched foods may benefit human health

Selenium is an essential nutrient and deficient intakes compromise health in domestic animals and humans. A recommended dietary allowance (RDA) of 55 µg d^?1 has been set for adult males and females in the United States; most North Americans consume more than this amount, but many residents of Europe, Asia and Africa consume less. While there are very few reports of outright Se deficiency in people consuming mixed Western diets that have Se intakes below the RDA, there is evidence that dietary intakes of selenium greater than the requirement may help reduce the risk of cancer, especially prostate cancer, to men. Selenium metabolism depends on the chemical form of Se in the diet, and some forms are better for some actions (e.g., cancer reduction) than other forms. Foods may contain different amounts and chemical forms of Se; consequently the benefits of Se may depend on the particular foods consumed. There are many reports of the chemistry and health benefits of Se from plant foods; animal foods also contain Se, but there are fewer reported studies. Fully understanding the health benefits of Se that may be gained by consumption of Se‐enriched foods will require multidisciplinary approaches by teams of medical researchers, chemists, nutritionists, and agricultural scientists. Copyright © 2007 Society of Chemical Industry     

Chiral Selenium Nanotherapeutics Regulates Selenoproteins to Attenuate Glucocorticoid-Induced Osteoporosis

Glucocorticoid (GC)-induced osteoporosis (GIO) is a concurrent disease commonly appeared in chronic inflammatory and autoimmune disease patients. Stereoselective recognition between chiral drugs and homochiral biological molecules could directly affect their distribution, adhesion and transport. Herein, trace element selenium (Se) with bone formation-regulating activity, is employed to construct cysteine-decorated chiral nanoparticles (Cys@SeNPs) to attenuate GIO. Interestingly, comparing with the racemic (DL-Cys@SeNPs) and D-Cys@SeNPs, the L-Cys@SeNPs displays higher uptake in osteoblast cells and could lessen reactive oxygen species overproduction to block dexamethasone (Dex)-induced osteoblasts cells apoptosis. Intracellular L-Cys@SeNPs could be predominantly transformed to selenocystine to upregulate the expression levels of antioxidative selenoproteins to effectively scavenge Dex-induced excessive ROS accumulation in osteoblasts, and thus reduce the undesirable apoptosis through activating Wnt/β-catenin pathway. Consistently, L-Cys@SeNPs significantly alleviates the main osteoporosis symptoms of bone trabeculae destruction and decreased bone density in vivo, and also reduces the weight gain and fatty liver formation in Dex-exposed mice, thus suppressing the overall side effects of Dex. This study not only demonstrates an effective strategy for treatment of GIO by using chiral Se nanomedicine, but also elucidates the important roles of selenoproteins in alleviating osteoporosis, which could help for future Se-based drug design through chirality control engineering.