The Interaction between Dietary Selenium Intake and Genetics in Determining Cancer Risk and Outcome

Kadkol, Shrinidhi; Diamond, Alan M.

doi:10.3390/nu12082424

Cited by 18 publications

(11 citation statements)

References 99 publications

(125 reference statements)

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“…Notably, evolutionary selection of certain genotypes may have enabled a better adaptation to nutritional restrictions, and render subjects less sensitive to poor supply in a Se-deficient environment [34]. A full overview of the potential interactions between variations in Se-related genes and health issues can be found elsewhere [35][36][37]. Notably, certain genotypes associate with autoimmune disease (AID) risk and autoantibody titers, e.g., in selenoprotein S (SELENOS) [38] or selenoprotein P (SELENOP) [39].…”

Section: Model Systems Inherited Diseases and Hierarchical Selenium Supplymentioning

confidence: 99%

Selenium Deficiency Due to Diet, Pregnancy, Severe Illness, or COVID-19—A Preventable Trigger for Autoimmune Disease

Schomburg

2021

IJMS

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The trace element selenium (Se) is an essential part of the human diet; moreover, increased health risks have been observed with Se deficiency. A sufficiently high Se status is a prerequisite for adequate immune response, and preventable endemic diseases are known from areas with Se deficiency. Biomarkers of Se status decline strongly in pregnancy, severe illness, or COVID-19, reaching critically low concentrations. Notably, these conditions are associated with an increased risk for autoimmune disease (AID). Positive effects on the immune system are observed with Se supplementation in pregnancy, autoimmune thyroid disease, and recovery from severe illness. However, some studies reported null results; the database is small, and randomized trials are sparse. The current need for research on the link between AID and Se deficiency is particularly obvious for rheumatoid arthritis and type 1 diabetes mellitus. Despite these gaps in knowledge, it seems timely to realize that severe Se deficiency may trigger AID in susceptible subjects. Improved dietary choices or supplemental Se are efficient ways to avoid severe Se deficiency, thereby decreasing AID risk and improving disease course. A personalized approach is needed in clinics and during therapy, while population-wide measures should be considered for areas with habitual low Se intake. Finland has been adding Se to its food chain for more than 35 years—a wise and commendable decision, according to today’s knowledge. It is unfortunate that the health risks of Se deficiency are often neglected, while possible side effects of Se supplementation are exaggerated, leading to disregard for this safe and promising preventive and adjuvant treatment options. This is especially true in the follow-up situations of pregnancy, severe illness, or COVID-19, where massive Se deficiencies have developed and are associated with AID risk, long-lasting health impairments, and slow recovery.

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Section: Model Systems Inherited Diseases and Hierarchical Selenium Supplymentioning

confidence: 99%

Selenium Deficiency Due to Diet, Pregnancy, Severe Illness, or COVID-19—A Preventable Trigger for Autoimmune Disease

Schomburg

2021

IJMS

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“…Polymorphisms in selenoproteins are associated with variations in protein levels and pose a cancer risk to the system. These types of polymorphisms are seen in the 3'UTR of mRNA (Kadkol and Diamond, 2020). Studies have also reported an inverse relationship between cancer risk and Sepp1 levels (Cui et al, 2017).…”

Section: Selenoprotein Pmentioning

confidence: 99%

Chemopreventive and Anticancer Property of Selenoproteins in Obese Breast Cancer

et al. 2021

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Obesity is a significant risk factor for various cancers including breast cancer resulting in an increased risk of recurrence as well as morbidity and mortality. Extensive studies on various pathways have been successful in establishing a biological relationship between obesity and breast cancer. The molecular classification of breast cancer includes five groups each having different responses to treatment. Increased levels of inflammatory cytokines seen in obese conditions drive the pro-proliferative pathways, such as the influx of macrophages, angiogenesis, and antiapoptotic pathways. Increased peripheral aromatization of androgens by aromatase increases the circulating estrogen levels which are also responsible for the association of obesity with breast cancer. Also, increased oxidative stress due to chronic low-grade inflammation in obese women plays an important role in carcinogenesis. Despite the availability of safe and effective treatment options for breast cancer, obese women are at increased risk of adverse outcomes including treatment-related toxicities. In the recent decade, selenium compounds have gained substantial interest as chemopreventive and anticancer agents. The chemical derivatives of selenium include inorganic and organic compounds that exhibit pro-oxidant properties and alter cellular redox homeostasis. They target more than one metabolic pathway by thiol modifications, induction of reactive oxygen species, and chromatin modifications to exert their chemopreventive and anticancer activities. The primary functional effectors of selenium that play a significant role in human homeostasis are selenoproteins like glutathione peroxidase, thioredoxin reductase, iodothyronine deiodinases, and selenoprotein P. Selenoproteins play a significant role in adipose tissue physiology by modulating preadipocyte proliferation and adipogenic differentiation. They correlate negatively with body mass index resulting in increased oxidative stress that may lead to carcinogenesis in obese individuals. Methylseleninic acid effectively suppresses aromatase activation thus reducing the estrogen levels and acting as a breast cancer chemopreventive agent. Adipose-derived inflammatory mediators influence the selenium metabolites and affect the proliferation and metastatic properties of cancer cells. Recently selenium nanoparticles have shown potent anticancer activity which may lead to a major breakthrough in the management of cancers caused due to multiple pathways. In this review, we discuss the possible role of selenoproteins as chemopreventive and an anticancer agent in obese breast cancer.

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“…Selenium (Se) is an essential micronutrient; trace amounts are necessary for the function of the human body and it is mainly obtained through diet and/or nutritional supplements [ 4 ]. Se is a component of the selenoproteins (mostly in the form of amino acid selenocysteine) that participate in a wide range of cellular physiological processes [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Novel N,N′-Disubstituted Selenoureas as Potential Antioxidant and Cytotoxic Agents

et al. 2021

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A series of 30 novel N,N disubstituted selenoureas were synthesized, characterized, and their antioxidant ability was tested using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid (ABTS) assays. Additionally, their cytotoxic activity was tested in vitro in a panel of three different cancer (breast, lung and colon) and two normal cell lines. Each selenourea entity contains a para-substituted phenyl ring with different electron-withdrawing and electron-donating groups, and different aliphatic and aromatic nuclei. All of the synthesized selenoureas present antioxidant capacity at high concentrations in the DPPH assay, and three of them (2b, 2c and 2d) showed greater radical scavenging capacity than ascorbic acid at lower concentrations. These results were confirmed by the ABTS assay, where these novel selenoureas present even higher antioxidant capacity than the reference compound Trolox. On the other hand, 10 selenoureas present IC50 values below 10 µM in at least one cancer cell line, resulting in the adamantyl nucleus (6a–6e), the most interesting in terms of activity and selectivity. Outstanding results were found for selenourea 6c, tested in the NCI60 cell line panel and showing an average GI50 of 1.49 µM for the 60 cell lines, and LC50 values ranging from 9.33 µM to 4.27 µM against 10 of these cancer cell lines. To gain insight into its anticancer activity mechanism, we investigated the cell cycle progression of the promising compound 6c, as well as the type of programmed-cell death in a colon cancer cell line it provokes (HT-29). Compound 6c provoked S phase cell cycle arrest and the induction of cell death was independent of caspase activation, suggesting autophagy, though this assertion requires additional studies. Overall, we envision that this compound can be further developed for the potential treatment of colon cancer.

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The Interaction between Dietary Selenium Intake and Genetics in Determining Cancer Risk and Outcome

Cited by 18 publications

References 99 publications

Selenium Deficiency Due to Diet, Pregnancy, Severe Illness, or COVID-19—A Preventable Trigger for Autoimmune Disease

Selenium Deficiency Due to Diet, Pregnancy, Severe Illness, or COVID-19—A Preventable Trigger for Autoimmune Disease

Chemopreventive and Anticancer Property of Selenoproteins in Obese Breast Cancer

Novel N,N′-Disubstituted Selenoureas as Potential Antioxidant and Cytotoxic Agents

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