Selenium as a Bioactive Micronutrient in the Human Diet and Its Cancer Chemopreventive Activity

Abstract

This review answers the question of why selenium is such an important trace element in the human diet. Daily dietary intake of selenium and its content in various food products is discussed in this paper, as well as the effects of its deficiency and excess in the body. Moreover, the biological activity of selenium, which it performs mainly through selenoproteins, is discussed. These specific proteins are responsible for thyroid hormone management, fertility, the aging process, and immunity, but their key role is to maintain a redox balance in cells. Furthermore, taking into account world news and the current SARS-CoV-2 virus pandemic, the impact of selenium on the course of COVID-19 is also discussed. Another worldwide problem is the number of new cancer cases and cancer-related mortality. Thus, the last part of the article discusses the impact of selenium on cancer risk based on clinical trials (including NPC and SELECT), systematic reviews, and meta-analyses. Additionally, this review discusses the possible mechanisms of selenium action that prevent cancer development.

The Role of Selenium in Pathologies: An Updated Review

“…Selenium exerts its chemo-preventive effect primarily by maintaining the correct redox homeostasis and an error-free protein folding, mainly through selenoproteins such as glutathione peroxidases (GPxs), thioredoxin reductases (TrxRs) and selenoprotein P (SelP, SeP or SELENOP), that prevents DNA oxidative mutagenic stress [ 55 ]. Other functions include the modulation of gene expression, the redox and hormonal regulation of metabolism, and a role in DNA repairing and cell-signalling pathways.…”

“…Beyond selenoproteins, different metabolites act at different stages for tumour prevention. Methylselenol, generated in the body from inorganic or organic selenium compounds, is arguably one of the most important among such metabolites [ 55 , 56 ]. Active selenium metabolites include: (i) selenodiglutathione (GS-Se-SG), the reductive metabolite of oxidized inorganic salts (selenite, selenate); (ii) selenomethionine (SeMet), a selenated methionine analogue which represents the main form of selenium in food; (iii) hydrogen selenide (H 2 Se), the common intermediate of the reductive pathway and the catabolism of seleno-amino acids; (iv) methylated metabolites of selenide such as CH 3 SeH (methylselenol), (CH 3 ) 3 Se + (trimethylselenonium), CH 3 SeCys (methylseleno-cyeteine) and CH 3 SeO 2 H (methylseleninic acid).…”

“…Particularly, the interaction between genetic factors and the dietary selenium intake seems to be effective in determining cancer risk and outcome via the metabolism of pivotal selenoproteins such as SelP, SelF (Selenoprotein F), GPx4, and GPx1 [ 66 ]. Some polymorphisms may be associated with the increase of aggressive prostate cancer, breast cancer and colorectal cancer [ 55 ].…”

Antitumor Effects of Selenium

“…These functions may be explained by the roles of selenoproteins, such as GPx, TrxR, selenoprotein P, and selenoprotein W [ 35 , 60 , 61 , 62 ]. The roles of these enzymes have been extensively reviewed in relation to their potential functions in physiological phenomena as antioxidant defense, redox regulation of cytokine, differentiation, apoptosis, and tumorigenesis [ 63 ]. Glutathione-peroxidase and other selenoproteins can reduce hydrogen peroxide and phospholipid peroxides, thereby blocking the propagation of free radicals and reactive oxygen species, and they can also reduce hydrogen peroxides intermediate in the cyclooxygenase and lipoxygenase pathways diminishing the production of inflammatory prostaglandin and leukotrienes [ 64 ].…”

Pharmaceutical and Safety Profile Evaluation of Novel Selenocompounds with Noteworthy Anticancer Activity

“…Additionally, it can act as a free radical scavenger, antitumor, and antiaging agent [3]. Moreover, selenium is a micronutrient with potential applications in the treatment or prevention of specific diseases, including cardiovascular disorders, thyroid and neurodegenerative diseases, depression, acute pancreatitis (AP), viral infections (such as HIV), and cancer [4,5]. In all these pharmaceutical applications, the gap between toxic and therapeutic doses is narrow [6].…”