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Luo Q, Bai X, Li X, Liu C. The role and mechanism of selenium in the prevention and progression of hepatocellular carcinoma. Front Oncol 2025; 15:1557233. [PMID: 40182029 PMCID: PMC11965637 DOI: 10.3389/fonc.2025.1557233] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2025] [Accepted: 03/05/2025] [Indexed: 04/05/2025] Open
Abstract
Hepatocellular carcinoma (HCC) represents the most prevalent form of liver cancer. Despite notable advancements in therapeutic strategies, HCC continues to pose significant public health challenges due to its rising incidence and high mortality rates worldwide. Selenium is an essential trace element that playing a critical role in human health. Recent studies have highlighted its potential preventive and therapeutic benefits in the context of HCC. However, some in vitro and in vivo investigations have yielded inconsistent results, and the mechanisms by which selenium influences HCC are still not completely clear. This review begins by providing an extensive evaluation of the effects and mechanisms of selenium on the primary risk factors associated with HCC, including viral infections, metabolic abnormalities, and lifestyle factors. Subsequently, we outline the roles and mechanisms by which selenium influences the proliferation, metastasis, and immune microenvironment of HCC. Finally, we emphasize the imperative for further investigation into the optimal dosage and forms of selenium, as well as its effects on the HCC microenvironment, to inform the development of effective clinical strategies. This review thus provides a foundational framework for the potential clinical application of selenium in the treatment of HCC.
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Affiliation(s)
- Qinying Luo
- BioBank, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Xiaofang Bai
- Department of Ultrasonography, The First Affiliated Hospital, Xi’an Jiaotong University, Xi’an, China
| | - Xiaojiao Li
- BioBank, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Chang Liu
- Department of Clinical Laboratory, Gongli Hospital of Shanghai Pudong, Shanghai, China
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Han F, Liu Y, Wang Q, Huang Z. Dietary Reference Intakes of Selenium for Chinese Residents. J Nutr 2025:S0022-3166(25)00014-8. [PMID: 39800311 DOI: 10.1016/j.tjnut.2025.01.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2024] [Revised: 01/06/2025] [Accepted: 01/07/2025] [Indexed: 01/29/2025] Open
Abstract
The plasma selenoprotein P (SELENOP) concentration leveling out was thought to represent saturation of the functional selenium body pool and an appropriate supply of selenium to all tissues, indicating that the necessary amount of selenium had been supplied. Based on the selenium intake when SELENOP reaches saturation, the estimated average requirement of selenium was set as 50 μg/d, and the recommended nutrient intake was 60 μg/d for Chinese general population. According to a recent study, "lactating Chinese women with the optimal daily selenium intake" was defined, and the adequate intake of 0‒6-mo-old infants was set as 15 μg/d, whereas 20 μg/d was calculated for 7‒12 mo old infants. Considering the negative health effects of intake of excessive nutrient levels of selenium, we recommend reducing the tolerable upper intake level (UL) for adults from 400 to 255 μg/d based on the results of the Selenium and Vitamin E Cancer Prevention Trial (SELECT). The SELECT trial is a key basis for setting selenium's UL. It has a large sample size and long-term design. It rigorously measures selenium intake and monitors multiple health endpoints precisely. Also, with proper control groups, it effectively determines the threshold of adverse effects, enhancing the reliability of UL determination.
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Affiliation(s)
- Feng Han
- National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, NHC Key Laboratory of Public Nutrition and Health, Beijing, China
| | - Yiqun Liu
- National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, NHC Key Laboratory of Public Nutrition and Health, Beijing, China
| | - Qin Wang
- National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, NHC Key Laboratory of Public Nutrition and Health, Beijing, China
| | - Zhenwu Huang
- National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, NHC Key Laboratory of Public Nutrition and Health, Beijing, China.
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3
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Bai S, Zhang M, Tang S, Li M, Wu R, Wan S, Chen L, Wei X, Feng S. Effects and Impact of Selenium on Human Health, A Review. Molecules 2024; 30:50. [PMID: 39795109 PMCID: PMC11721941 DOI: 10.3390/molecules30010050] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2024] [Revised: 12/16/2024] [Accepted: 12/23/2024] [Indexed: 01/13/2025] Open
Abstract
Selenium (Se) is an essential trace element that is crucial for human health. As a key component of various enzymes and proteins, selenium primarily exerts its biological functions in the form of selenoproteins within the body. Currently, over 30 types of selenoproteins have been identified, with more than 20 of them containing selenocysteine residues. Among these, glutathione peroxidases (GPXs), thioredoxin reductases (TrxRs), and iodothyronine deiodinases (DIOs) have been widely studied. Selenium boasts numerous biological functions, including antioxidant properties, immune system enhancement, thyroid function regulation, anti-cancer effects, cardiovascular protection, reproductive capability improvement, and anti-inflammatory activity. Despite its critical importance to human health, the range between selenium's nutritional and toxic doses is very narrow. Insufficient daily selenium intake can lead to selenium deficiency, while excessive intake carries the risk of selenium toxicity. Therefore, selenium intake must be controlled within a relatively precise range. This article reviews the distribution and intake of selenium, as well as its absorption and metabolism mechanisms in the human body. It also explores the multiple biological functions and mechanisms of selenium in maintaining human health. The aim is to provide new insights and evidence for further elucidating the role of selenium and selenoproteins in health maintenance, as well as for future nutritional guidelines and public health policies.
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Affiliation(s)
- Song Bai
- Guizhou Industry Polytechnic College, Guiyang 550008, China; (S.B.); (M.L.); (R.W.); (S.W.); (L.C.)
- School of Chemical Engineering, Guizhou Institute of Technology, Guiyang 550003, China; (M.Z.); (X.W.); (S.F.)
- National Key Laboratory of Green Pesticide, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guizhou University, Guiyang 550025, China
| | - Miaohe Zhang
- School of Chemical Engineering, Guizhou Institute of Technology, Guiyang 550003, China; (M.Z.); (X.W.); (S.F.)
| | - Shouying Tang
- Guizhou Industry Polytechnic College, Guiyang 550008, China; (S.B.); (M.L.); (R.W.); (S.W.); (L.C.)
| | - Miao Li
- Guizhou Industry Polytechnic College, Guiyang 550008, China; (S.B.); (M.L.); (R.W.); (S.W.); (L.C.)
| | - Rong Wu
- Guizhou Industry Polytechnic College, Guiyang 550008, China; (S.B.); (M.L.); (R.W.); (S.W.); (L.C.)
| | - Suran Wan
- Guizhou Industry Polytechnic College, Guiyang 550008, China; (S.B.); (M.L.); (R.W.); (S.W.); (L.C.)
| | - Lijun Chen
- Guizhou Industry Polytechnic College, Guiyang 550008, China; (S.B.); (M.L.); (R.W.); (S.W.); (L.C.)
| | - Xian Wei
- School of Chemical Engineering, Guizhou Institute of Technology, Guiyang 550003, China; (M.Z.); (X.W.); (S.F.)
| | - Shuang Feng
- School of Chemical Engineering, Guizhou Institute of Technology, Guiyang 550003, China; (M.Z.); (X.W.); (S.F.)
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Maleczek M, Reszeć-Giełażyn J, Szymulewska-Konopko K. Beneficial Effects of Selenium and Its Supplementation on Carcinogenesis and the Use of Nanoselenium in the Treatment of Malignant Tumors. Int J Mol Sci 2024; 25:11285. [PMID: 39457066 PMCID: PMC11508626 DOI: 10.3390/ijms252011285] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2024] [Revised: 10/09/2024] [Accepted: 10/12/2024] [Indexed: 10/28/2024] Open
Abstract
Selenium was recognized as a non-toxic element in the second half of the 20th century. Since then, the positive impact of selenium on the functioning of the human body has been noticed. It has been shown that low levels of selenium in the body are significantly associated with a higher risk of developing cancer. Selenium acts as an antioxidant and inhibits the proliferation of cancer cells. It has been shown that selenium supplementation may contribute to reducing the risk of DNA mutations and carcinogenesis. Nanomedicine has become very helpful in both the diagnosis and treatment of cancer. Due to its anticancer properties, selenium is used in nanotechnology as selenium nanoparticles.
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Affiliation(s)
| | - Joanna Reszeć-Giełażyn
- Department of Medical Pathomorphology, Medical University of Białystok, 15-269 Białystok, Poland; (M.M.)
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Jahankhani K, Taghipour N, Mashhadi Rafiee M, Nikoonezhad M, Mehdizadeh M, Mosaffa N. Therapeutic effect of trace elements on multiple myeloma and mechanisms of cancer process. Food Chem Toxicol 2023; 179:113983. [PMID: 37567355 DOI: 10.1016/j.fct.2023.113983] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2023] [Revised: 07/09/2023] [Accepted: 08/07/2023] [Indexed: 08/13/2023]
Abstract
In the human body, trace elements and other micronutrients play a vital role in growth, health and immune system function. The trace elements are Iron, Manganese, Copper, Iodine, Zinc, Cobalt, Fluoride, and Selenium. Estimating the serum levels of trace elements in hematologic malignancy patients can determine the severity of the tumor. Multiple myeloma (MM) is a hematopoietic malignancy and is characterized by plasma cell clonal expansion in bone marrow. Despite the advances in treatment methods, myeloma remains largely incurable. In addition to conventional medicine, treatment is moving toward less expensive noninvasive alternatives. One of the alternative treatments is the use of dietary supplements. In this review, we focused on the effect of three trace elements including iron, zinc and selenium on important mechanisms such as the immune system, oxidative and antioxidant factors and cell cycle. Using some trace minerals in combination with approved drugs can increase patients' recovery speed. Trace elements can be used as not only a preventive but also a therapeutic tool, especially in reducing inflammation in hematological cancers such as multiple myeloma. We hope that the prospect of the correct use of trace element supplements in the future could be promising for the treatment of diseases.
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Affiliation(s)
- Kasra Jahankhani
- Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Niloofar Taghipour
- Medical Nanotechnology and Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | - Maryam Nikoonezhad
- Department of Immunology, School of Medicine, Tarbiat Modarres University, Tehran, Iran
| | - Mahshid Mehdizadeh
- Hematopoietic Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Nariman Mosaffa
- Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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Shi J, Liu Z, Li W, Wang D. Selenium Donor Inhibited Hepatitis B Virus Associated Hepatotoxicity via the Apoptosis and Ferroptosis Pathways. Anal Cell Pathol (Amst) 2023; 2023:6681065. [PMID: 37680557 PMCID: PMC10482541 DOI: 10.1155/2023/6681065] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2023] [Revised: 07/05/2023] [Accepted: 07/19/2023] [Indexed: 09/09/2023] Open
Abstract
Methods The serum selenium level was determined in 45 patients with HBV-positive HCC (HBV+-HCC group), 45 patients with chronic hepatitis B virus infection (CHB group), and 45 healthy cases (HC group). The sodium selenite (Na2SeO3)-treated HepG2.2.15 cells were used to observe the regulatory role of selenium on HBV replication. D-GalN/erastin-added HL7702 was used to determine the regulatory roles of Na2SeO3 on hepatotoxicity or hepatocyte ferroptosis. The wild-type (WT) C57BL/6 mice and HBx-Tg mice were received lipopolysaccharide (LPS)/D-GalN, together with or without Na2SeO3 administration for indicated period. Following euthanasia, the blood and liver tissue samples were collected, and specific markers were evaluated subsequently. Results The serum selenium level was downregulated in patients with HBV-positive HCC (HBV+-HCC group) (57.2 ± 22.5 μg/L vs. 91.8 ± 43.9 μg/L, P < 0.001), and its higher level could provide a better prognosis in these patients. The treatment using Na2SeO3, a selenium donor, at high concentration (5 μM), suppressed the HBV replication by about 50% in HepG2.2.15 cells (P < 0.001), through promoting apoptotic cell death and inhibiting cellular inhibitor of apoptosis proteins (cIAPs). In addition, low-dose (500 nM) Na2SeO3 could almost totally reversed the hepatotoxicity induced by hepatitis B virus X protein (HBx) (P < 0.001), which were the main causes of HCC in patients. Studies at the cellular levels showed that low-dose Na2SeO3 inhibited the HBx-related hepatotoxicity by blocking ferroptosis, and glutathione peroxidase 4 (GPX4) mediated this regulatory role. Mice model results confirmed that the treatment with Na2SeO3 could mitigated LPS/D-GalN-induced hepatic injury through ferroptosis pathways. Conclusion Selenium regulated the dual cell death in different HCC stages via different signaling pathways, which could partly explain the anti-HBV and anti-HCC properties of selenium.
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Affiliation(s)
- Jingdong Shi
- General Surgery Department, Beijing Tian Tan Hospital, Capital Medical University, Beijing 100050, China
| | - Zhen Liu
- The Eighth Medical Center, Chinese PLA General Hospital, Beijing 100091, China
| | - Weina Li
- Medical Research and Laboratory Diagnostic Center, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250013, Shandong, China
| | - Di Wang
- The Eighth Medical Center, Chinese PLA General Hospital, Beijing 100091, China
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Sun H, Long J, Zuo B, Li Y, Song Y, Yu M, Xun Z, Wang Y, Wang X, Sang X, Zhao H. Development and validation of a selenium metabolism regulators associated prognostic model for hepatocellular carcinoma. BMC Cancer 2023; 23:451. [PMID: 37202783 PMCID: PMC10197375 DOI: 10.1186/s12885-023-10944-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Accepted: 05/10/2023] [Indexed: 05/20/2023] Open
Abstract
BACKGROUND Selenium metabolism has been implicated in human health. This study aimed to identify a selenium metabolism regulator-based prognostic signature for hepatocellular carcinoma (HCC) and validate the role of INMT in HCC. METHODS Transcriptome sequencing data and clinical information related to selenium metabolism regulators in TCGA liver cancer dataset were analysed. Next, a selenium metabolism model was constructed by multiple machine learning algorithms, including univariate, least absolute shrinkage and selection operator, and multivariate Cox regression analyses. Then, the potential of this model for predicting the immune landscape of different risk groups was evaluated. Finally, INMT expression was examined in different datasets. After knockdown of INMT, cell proliferation and colony formation assays were conducted. RESULTS A selenium metabolism model containing INMT and SEPSECS was established and shown to be an independent predictor of prognosis. The survival time of low-risk patients was significantly longer than that of high-risk patients. These two groups had different immune environments. In different datasets, including TCGA, GEO, and our PUMCH dataset, INMT was significantly downregulated in HCC tissues. Moreover, knockdown of INMT significantly promoted HCC cell proliferation. CONCLUSIONS The current study established a risk signature of selenium metabolism regulators for predicting the prognosis of HCC patients. INMT was identified as a biomarker for poor prognosis of HCC.
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Affiliation(s)
- Huishan Sun
- Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
- Medical Research Center, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Junyu Long
- Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Bangyou Zuo
- Department of Hepatobiliary Surgery, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China Chengdu, Sichuan, China
| | - Yiran Li
- Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
- Medical Research Center, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Yu Song
- Department of Allergy, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Minghang Yu
- Beijing Institute of Infectious Diseases, Beijing, China
- Institute of Infectious Diseases, Beijing Key Laboratory of Emerging Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Ziyu Xun
- Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Yanyu Wang
- Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Xi Wang
- Beijing Institute of Infectious Diseases, Beijing, China.
- Institute of Infectious Diseases, Beijing Key Laboratory of Emerging Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
| | - Xinting Sang
- Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
| | - Haitao Zhao
- Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
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Zhang F, Li X, Wei Y. Selenium and Selenoproteins in Health. Biomolecules 2023; 13:biom13050799. [PMID: 37238669 DOI: 10.3390/biom13050799] [Citation(s) in RCA: 94] [Impact Index Per Article: 47.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2023] [Revised: 04/19/2023] [Accepted: 04/27/2023] [Indexed: 05/28/2023] Open
Abstract
Selenium is a trace mineral that is essential for health. After being obtained from food and taken up by the liver, selenium performs various physiological functions in the body in the form of selenoproteins, which are best known for their redox activity and anti-inflammatory properties. Selenium stimulates the activation of immune cells and is important for the activation of the immune system. Selenium is also essential for the maintenance of brain function. Selenium supplements can regulate lipid metabolism, cell apoptosis, and autophagy, and have displayed significant alleviating effects in most cardiovascular diseases. However, the effect of increased selenium intake on the risk of cancer remains unclear. Elevated serum selenium levels are associated with an increased risk of type 2 diabetes, and this relationship is complex and nonlinear. Selenium supplementation seems beneficial to some extent; however, existing studies have not fully explained the influence of selenium on various diseases. Further, more intervention trials are needed to verify the beneficial or harmful effects of selenium supplementation in various diseases.
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Affiliation(s)
- Fan Zhang
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
- Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
- Hubei Engineering Research Center for Immunological Diagnosis and Therapy of Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Xuelian Li
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
- Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
- Hubei Engineering Research Center for Immunological Diagnosis and Therapy of Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Yumiao Wei
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
- Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
- Hubei Engineering Research Center for Immunological Diagnosis and Therapy of Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
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Dobrzyńska M, Drzymała-Czyż S, Woźniak D, Drzymała S, Przysławski J. Natural Sources of Selenium as Functional Food Products for Chemoprevention. Foods 2023; 12:1247. [PMID: 36981172 PMCID: PMC10048267 DOI: 10.3390/foods12061247] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Revised: 03/13/2023] [Accepted: 03/13/2023] [Indexed: 03/17/2023] Open
Abstract
Cancer is one of the leading causes of death worldwide, the incidence of which is increasing annually. Interest has recently grown in the anti-cancer effect of functional foods rich in selenium (Se). Although clinical studies are inconclusive and anti-cancer mechanisms of Se are not fully understood, daily doses of 100-200 µg of Se may inhibit genetic damage and the development of cancer in humans. The anti-cancer effects of this trace element are associated with high doses of Se supplements. The beneficial anti-cancer properties of Se and the difficulty in meeting the daily requirements for this micronutrient in some populations make it worth considering the use of functional foods enriched in Se. This review evaluated studies on the anti-cancer activity of the most used functional products rich in Se on the European market.
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Affiliation(s)
| | - Sławomira Drzymała-Czyż
- Department of Bromatology, Poznan University of Medical Science, Rokietnicka 3 Street, 60-806 Poznan, Poland
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Yang M, Pei B, Hu Q, Li X, Fang X, Huang X, Yang Z, Chen J, He D, Sun G, Lv P, Wang L, Zhang Z, Lai L, Huang C. Effects of selenium supplementation on concurrent chemoradiotherapy in patients with cervical cancer: A randomized, double-blind, placebo-parallel controlled phase II clinical trial. Front Nutr 2023; 10:1094081. [PMID: 36819673 PMCID: PMC9932900 DOI: 10.3389/fnut.2023.1094081] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2022] [Accepted: 01/19/2023] [Indexed: 02/05/2023] Open
Abstract
Objective Selenium (Se) is an essential trace element and may affect cervical cancer occurrence and progression. The association between selenium supplementation and acute toxic reactions and clinical outcomes in patients with locally advanced cervical cancer treated with concurrent chemoradiotherapy remains unclear. The aim of this study was to determine the safety profile of add-on Se yeast and assess the potential of Se to ameliorate the hematologic toxicity of concurrent chemoradiotherapy in patients with cervical cancer. Methods Patients with Federation International of Gynecology and Obstetrics (FIGO) stage IIB cervical cancer who met all inclusion criteria were randomly assigned to either the experimental group or the control group. The experimental group received Se yeast tablets (100 μg Se, twice daily), while the control group received placebos (twice daily) for 5 weeks in total. All patients in both groups received standard treatment, including pelvic external irradiation, concurrent five cycles of chemotherapy, and brachytherapy. Measures included the incidence of myelosuppression, impairment of liver and kidney function, objective response rate (ORR), and blood Se concentrations before, during and after the treatment of the two groups. Results A total of 104 eligible patients were enrolled in the experimental group (n = 50) or the control group (n = 54). The ORR in the experimental group and control group were 96 and 94%, respectively (p = 0.47). The baseline levels of blood Se before treatment in the experimental and control groups were similar (58.34 ± 17.63 μg/L and 60.21 ± 18.42 μg/L, p = 0.60), but the concentrations became significantly different after course completion between the two groups (76.16 ± 24.47 μg/L and 57.48 ± 14.92 μg/L, respectively, p < 0.01). Se dramatically decreased the incidence of grade 3 myelosuppression (48% vs. 63%, p = 0.034) compared to the control group. In the subgroup of patients with moderately well-differentiated cervical cancer, the incidence of thrombocytopenia induced by concurrent chemoradiotherapy was lower in the experimental group than in the control group (53.8% vs. 78.9%, p < 0.01). However, no difference was observed in liver and kidney injuries between the two groups. Conclusion Supplementation with Se effectively increased blood Se levels in Se-inadequate cervical cancer patients. As an add-on to standard treatment, Se-yeast significantly decreased the hematologic toxicity of concurrent chemoradiotherapy.
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Affiliation(s)
- Mei Yang
- Department of Oncology, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi Clinical College of Wuhan University, Enshi, China,Department of Oncology, Yunfu People's Hospital, Yunfu, China
| | - Bo Pei
- Department of Oncology, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi Clinical College of Wuhan University, Enshi, China,Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Qiancheng Hu
- Department of Abdominal Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Xiaoying Li
- Hubei Selenium and Human Health Institute, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, China
| | - Xiping Fang
- Department of Oncology, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi Clinical College of Wuhan University, Enshi, China
| | - Xue Huang
- Department of Oncology, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi Clinical College of Wuhan University, Enshi, China
| | - Zunjing Yang
- Department of Oncology, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi Clinical College of Wuhan University, Enshi, China
| | - Jiaquan Chen
- Department of Oncology, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi Clinical College of Wuhan University, Enshi, China
| | - Du He
- Department of Oncology, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi Clinical College of Wuhan University, Enshi, China
| | - Guogen Sun
- Hubei Selenium and Human Health Institute, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, China
| | - Peng Lv
- Department of Oncology, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi Clinical College of Wuhan University, Enshi, China
| | - Li Wang
- Hubei Selenium and Human Health Institute, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, China
| | - Zixiong Zhang
- Hubei Selenium and Human Health Institute, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, China,*Correspondence: Zixiong Zhang, ; Lin Lai, ; Chuying Huang,
| | - Lin Lai
- Department of Oncology, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi Clinical College of Wuhan University, Enshi, China,*Correspondence: Zixiong Zhang, ; Lin Lai, ; Chuying Huang,
| | - Chuying Huang
- Department of Oncology, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi Clinical College of Wuhan University, Enshi, China,Hubei Selenium and Human Health Institute, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, China,Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China,*Correspondence: Zixiong Zhang, ; Lin Lai, ; Chuying Huang,
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Abstract
In this review, the relevance of selenium (Se) to viral disease will be discussed paying particular attention to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease (COVID-19). Se, the active centre in selenoproteins has an ongoing history of reducing the incidence and severity of viral infections. Host Se deficiency increased the virulence of RNA viruses such as influenza A and coxsackievirus B3, the latter of which is implicated in the development of Keshan disease in north-east China. Significant clinical benefits of Se supplementation have been demonstrated in HIV-1, in liver cancer linked to hepatitis B, and in Chinese patients with hantavirus that was successfully treated with oral sodium selenite. China is of particular interest because it has populations that have both the lowest and the highest Se status in the world. We found a significant association between COVID-19 cure rate and background Se status in Chinese cities; the cure rate continued to rise beyond the Se intake required to optimise selenoproteins, suggesting an additional mechanism. Se status was significantly higher in serum samples from surviving than non-surviving COVID-19 patients. As regards mechanism, SARS-CoV-2 may interfere with the human selenoprotein system; selenoproteins are important in scavenging reactive oxygen species, controlling immunity, reducing inflammation, ferroptosis and endoplasmic reticulum (ER) stress. We found that SARS-CoV-2 significantly suppressed mRNA expression of GPX4, of the ER selenoproteins, SELENOF, SELENOM, SELENOK and SELENOS and down-regulated TXNRD3. Based on the available data, both selenoproteins and redox-active Se species (mimicking ebselen, an inhibitor of the main SARS-CoV-2 protease that enables viral maturation within the host) could employ their separate mechanisms to attenuate virus-triggered oxidative stress, excessive inflammatory responses and immune-system dysfunction, thus improving the outcome of SARS-CoV-2 infection.
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Abstract
The rapid spread of new pathogens (SARS-CoV-2 virus) that negatively affect the human body has huge consequences for the global public health system and the development of the global economy. Appropriate implementation of new safety regulations will improve the functioning of the current model supervising the inhibition of the spread of COVID-19 disease. Compliance with all these standards will have a key impact on the health behavior of individual social groups. There have been demonstrably effective treatments that proved to be effective but were rapidly dismissed for unknown reasons, such as ivermectin and hydroxychloroquine. Various measures are used in the world to help inhibit its development. The properties of this element provide hope in preventing the development of the SARS-CoV-2 virus. The aim of this review is to synthesize the latest literature data and to present the effect of sodium selenite in reducing the incidence of COVID-19 disease.
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Affiliation(s)
- Marek Kieliszek
- Department of Food Biotechnology and Microbiology, Institute of Food Sciences, Warsaw University of Life Sciences-SGGW, Nowoursynowska 159 C, 02-776, Warsaw, Poland.
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13
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Saranya T, Kavithaa K, Paulpandi M, Ramya S, Winster SH, Mani G, Dhayalan S, Balachandar V, Narayanasamy A. The creation of selenium nanoparticles decorated with troxerutin and their ability to adapt to the tumour microenvironment have therapeutic implications for triple-negative breast cancer. NEW J CHEM 2023. [DOI: 10.1039/d2nj05671b] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/11/2023]
Abstract
The unique use of selenium–troxerutin nanoconjugates as an effective management therapy for treating TNBC.
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Affiliation(s)
- Thiruvenkataswamy Saranya
- Disease Proteomics Laboratory, Department of Zoology, Bharathiar University, Coimbatore 641046, TN, India
| | - Krishnamoorthy Kavithaa
- Department of Biotechnology, Hindusthan College of Arts and Science, Coimbatore 641028, TN, India
| | - Manickam Paulpandi
- Disease Proteomics Laboratory, Department of Zoology, Bharathiar University, Coimbatore 641046, TN, India
| | - Sennimalai Ramya
- Disease Proteomics Laboratory, Department of Zoology, Bharathiar University, Coimbatore 641046, TN, India
- Department of Zoology, PSGR Krishnammal College for Women, Coimbatore 641004, Tamil Nadu, India
| | - Sureshbabu Harysh Winster
- Disease Proteomics Laboratory, Department of Zoology, Bharathiar University, Coimbatore 641046, TN, India
| | - Geetha Mani
- Department of Microbiology, Faculty of Science, Annamalai University, TN, India
| | - Sangeetha Dhayalan
- Department of Microbiology, Faculty of Science, Annamalai University, TN, India
| | - Vellingiri Balachandar
- Stem Cell Laboratory, Department of Human Genetics and Molecular Biology, Bharathiar University, Coimbatore 641046, TN, India
- Stem cell and Regenerative Medicine/Translational Research, Department of Zoology, School of Basic Sciences, Central University of Punjab, Bathinda, Punjab 151401, India
| | - Arul Narayanasamy
- Disease Proteomics Laboratory, Department of Zoology, Bharathiar University, Coimbatore 641046, TN, India
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14
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Blockage of Nrf2 and autophagy by L-selenocystine induces selective death in Nrf2-addicted colorectal cancer cells through p62-Keap-1-Nrf2 axis. Cell Death Dis 2022; 13:1060. [PMID: 36539411 PMCID: PMC9768144 DOI: 10.1038/s41419-022-05512-2] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2022] [Revised: 12/08/2022] [Accepted: 12/12/2022] [Indexed: 12/24/2022]
Abstract
Persistent Nrf2 activation is typically noted in many cancers, including colorectal cancer (CRC), aiding cancer cells in overcoming growth stress and promoting cancer progression. Sustained Nrf2 activation, which is beneficial for cancer cells, is called "Nrf2 addiction"; it is closely associated with malignancy and poor prognosis in patients with cancer. However, Nrf2 inhibitors may have adverse effects on normal cells. Here, we found that the selenocompound L-selenocystine (SeC) is selectively cytotoxic in the Nrf2-addicted CRC cell line WiDr cells, but not in non-Nrf2-addicted mesenchymal stem cells (MSCs) and normal human colon cells. Another CRC cell line, C2BBe1, which harbored lower levels of Nrf2 and its downstream proteins were less sensitive to SeC, compared with the WiDr cells. We further demonstrated that SeC inhibited Nrf2 and autophagy activation in the CRC cells. Antioxidant GSH pretreatment partially rescued the CRC cells from SeC-induced cytotoxicity and Nrf2 and autophagy pathway inhibition. By contrast, SeC activated Nrf2 and autophagy pathway in non-Nrf2-addicted MSCs. Transfecting WiDr cells with Nrf2-targeting siRNA decreased persistent Nrf2 activation and alleviated SeC cytotoxicity. In KEAP1-knockdown C2BBe1 cells, Nrf2 pathway activation increased SeC sensitivity and cytotoxicity. In conclusion, SeC selectively attacks cancer cells with constitutively activated Nrf2 by reducing Nrf2 and autophagy pathway protein expression through the P62-Nrf2-antioxidant response element axis and eventually trigger cell death.
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15
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Yan S, Su H, Xia Y, Yan Z, Gao Y, Shi M, Liu H, Wen Y, Zhao Y, Chang Q. Association between blood selenium levels and gestational diabetes mellitus: A systematic review and meta-analysis. Front Nutr 2022; 9:1008584. [PMID: 36505252 PMCID: PMC9726795 DOI: 10.3389/fnut.2022.1008584] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Accepted: 10/31/2022] [Indexed: 11/24/2022] Open
Abstract
Introduction The association between blood (serum or plasma) selenium concentrations and gestational diabetes mellitus (GDM) has been evaluated in some studies. However, the reported findings are debatable, and only case-control and cross-sectional studies were included. Objective This research aimed to assess the association between blood selenium levels and GDM by analyzing existing literature. To provide a reference for the prevention and treatment of GDM, we included prospective studies which are not included in previous studies to collate more high-quality evidence and better test the etiological hypothesis between blood Se concentrations and GDM. Methods The PubMed, EMBASE, and Web of Science databases were retrieved for literature up to September 2022, and relevant references were manually searched. Raw data from relevant studies were extracted, and a random effect model was adopted for meta-analysis. The total effects were reported as weighted mean differences. All data were analyzed using Stata 16.0 software. Results Fourteen studies involving 890 pregnant women with GDM and 1618 healthy pregnant women were incorporated in the meta-analysis. Pregnancies with GDM had significantly lower blood selenium levels than those with normal glucose tolerance (weighted mean difference = -8.11; 95% confidence interval: -12.68 to -3.54, P = 0.001). Subgroup analyses showed that the association between blood selenium levels and GDM was consistent in the residents of Asia and Africa, but not in European. This trend was significant in the second and third trimester subgroups, but not in the first trimester subgroup. Articles published in 2006-2015 also showed this trend, but those published before 2005 and 2016-2019 did not show significant results. This difference was evident in non-prospective studies, but not significant in prospective studies. Studies using the Carpenter and Coustan diagnostic criteria were consistent with this trend, whereas studies using other diagnostic criteria found no differences. In addition, in terms of blood selenium measurement methods, atomic absorption spectrometry showed more significant differences than other methods. In the subgroup analysis based on the sample size of included studies and the quality of the studies, each subgroup showed statistical differences. Conclusion Lower blood selenium concentrations are associated with GDM as shown in our study. Therefore, supplementing an appropriate amount of selenium may be helpful for GDM prevention and treatment.
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Affiliation(s)
- Shuai Yan
- Liaoning Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China,Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Han Su
- Liaoning Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China,Department of Health Management, Shengjing Hospital of China Medical University, Shenyang, China
| | - Yang Xia
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Zixuan Yan
- Liaoning Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China,Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Yitao Gao
- Liaoning Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China,Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Mengyuan Shi
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Huiyuan Liu
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Yu Wen
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Yuhong Zhao
- Liaoning Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China,Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China,Yuhong Zhao,
| | - Qing Chang
- Liaoning Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China,Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China,*Correspondence: Qing Chang,
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16
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Anti-hepatitis B virus activity of food nutrients and potential mechanisms of action. Ann Hepatol 2022:100766. [PMID: 36179798 DOI: 10.1016/j.aohep.2022.100766] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Accepted: 09/21/2022] [Indexed: 02/04/2023]
Abstract
Hepatitis B virus (HBV) is endemic in many parts of the world and is a significant cause of chronic liver damage and hepatocellular carcinoma. HBV therapeutics vary according to the disease stage. The best therapeutic option for patients with end-stage liver disease is liver transplantation, while for chronic patients, HBV infection is commonly managed using antivirals (nucleos(t)ides analogs or interferons). However, due to the accessibility issues and the high cost of antivirals, most HBV patients do not have access to treatment. These complications have led researchers to reconsider treatment approaches, such as nutritional therapy. This review summarizes the nutrients reported to have antiviral activity against HBV and their possible mechanism of action. Recent studies suggest resveratrol, vitamin E, lactoferrin, selenium, curcumin, luteolin-7-O-glucoside, moringa extracts, chlorogenic acid, and epigallocatechin-3-gallate may be beneficial for patients with hepatitis B. The anti-HBV effect of most of these nutrients has been analyzed in vitro and in animal models. Different antiviral and hepatoprotective mechanisms have been proposed for these nutrients, such as the activation of antioxidant and anti-inflammatory pathways, regulation of metabolic homeostasis, epigenetic control, activation of the p53 gene, inhibition of oncogenes, inhibition of virus entry, and induction of autophagosomes. In conclusion, scientific evidence indicates that HBV replication, transcription, and expression of viral antigens can be affected directly by nutrients. In the future, these nutrients may be considered to develop appropriate nutritional management for patients with hepatitis B.
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Zhang X, Hong R, Bei L, Hu Z, Yang X, Song T, Chen L, Meng H, Niu G, Ke C. SELENBP1 inhibits progression of colorectal cancer by suppressing epithelial–mesenchymal transition. Open Med (Wars) 2022; 17:1390-1404. [PMID: 36117772 PMCID: PMC9438969 DOI: 10.1515/med-2022-0532] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Revised: 06/19/2022] [Accepted: 07/11/2022] [Indexed: 01/13/2023] Open
Abstract
Selenium-binding protein 1 (SELENBP1) is frequently dysregulated in various malignancies including colorectal cancer (CRC); however, its roles in progression of CRCs and the underlying mechanism remain to be elucidated. In this study, we compared the expression of SELENBP1 between CRCs and colorectal normal tissues (NTs), as well as between primary and metastatic CRCs; we determined the association between SELENBP1 expression and CRC patient prognoses; we conducted both in vitro and in vivo experiments to explore the functional roles of SELENBP1 in CRC progression; and we characterized the potential underlying mechanisms associated with SELENBP1 activities. We found that the expression of SELENBP1 was significantly and consistently decreased in CRCs than that in adjacent NTs, while significantly and frequently decreased in metastatic than primary CRCs. High expression of SELENBP1 was an independent predictor of favorable prognoses in CRC patients. Overexpression of SELENBP1 suppressed, while silencing of SELENBP1 promoted cell proliferation, migration and invasion, and in vivo tumorigenesis of CRC. Mechanically, SELENBP1 may suppress CRC progression by inhibiting the epithelial–mesenchymal transition.
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Affiliation(s)
- Xiaotian Zhang
- Department of General Surgery, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, 200240, P.R. China
| | - Runqi Hong
- Department of General Surgery, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, 200240, P.R. China
| | - Lanxin Bei
- Department of Animal Science, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, 200240, China
| | - Zhiqing Hu
- Department of General Surgery, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, 200240, P.R. China
| | - Ximin Yang
- Department of Radiology, Dongying New District Hospital, Dongying, Shandong Province, 257000, P.R. China
| | - Tao Song
- Department of General Surgery, Shanghai Fifth People’s Hospital, Fudan University, 801 Heqing Road, Minhang District, Shanghai, 200240, P.R. China
| | - Liang Chen
- Department of General Surgery, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, 200240, P.R. China
| | - He Meng
- Department of Animal Science, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, 200240, China
| | - Gengming Niu
- Department of General Surgery, Shanghai Fifth People’s Hospital, Fudan University, 801 Heqing Road, Minhang District, Shanghai, 200240, P.R. China
| | - Chongwei Ke
- Department of General Surgery, Shanghai Fifth People’s Hospital, Fudan University, 801 Heqing Road, Minhang District, Shanghai, 200240, P.R. China
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18
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Ehudin MA, Golla U, Trivedi D, Potlakayala SD, Rudrabhatla SV, Desai D, Dovat S, Claxton D, Sharma A. Therapeutic Benefits of Selenium in Hematological Malignancies. Int J Mol Sci 2022; 23:ijms23147972. [PMID: 35887320 PMCID: PMC9323677 DOI: 10.3390/ijms23147972] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2022] [Revised: 07/09/2022] [Accepted: 07/12/2022] [Indexed: 12/14/2022] Open
Abstract
Supplementing chemotherapy and radiotherapy with selenium has been shown to have benefits against various cancers. This approach has also been shown to alleviate the side effects associated with standard cancer therapies and improve the quality of life in patients. In addition, selenium levels in patients have been correlated with various cancers and have served as a diagnostic marker to track the efficiency of treatments or to determine whether these selenium levels cause or are a result of the disease. This concise review presents a survey of the selenium-based literature, with a focus on hematological malignancies, to demonstrate the significant impact of selenium in different cancers. The anti-cancer mechanisms and signaling pathways regulated by selenium, which impart its efficacious properties, are discussed. An outlook into the relationship between selenium and cancer is highlighted to guide future cancer therapy development.
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Affiliation(s)
- Melanie A. Ehudin
- Division of Hematology and Oncology, Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA; (M.A.E.); (S.D.)
| | - Upendarrao Golla
- Division of Hematology and Oncology, Department of Medicine, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA; (U.G.); (D.C.)
- Penn State Cancer Institute, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA; (D.T.); (D.D.)
| | - Devnah Trivedi
- Penn State Cancer Institute, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA; (D.T.); (D.D.)
| | - Shobha D. Potlakayala
- Department of Biological Sciences, School of Science Engineering and Technology, Penn State Harrisburg, Middletown, PA 17057, USA; (S.D.P.); (S.V.R.)
| | - Sairam V. Rudrabhatla
- Department of Biological Sciences, School of Science Engineering and Technology, Penn State Harrisburg, Middletown, PA 17057, USA; (S.D.P.); (S.V.R.)
| | - Dhimant Desai
- Penn State Cancer Institute, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA; (D.T.); (D.D.)
- Department of Pharmacology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
| | - Sinisa Dovat
- Division of Hematology and Oncology, Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA; (M.A.E.); (S.D.)
| | - David Claxton
- Division of Hematology and Oncology, Department of Medicine, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA; (U.G.); (D.C.)
- Penn State Cancer Institute, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA; (D.T.); (D.D.)
| | - Arati Sharma
- Division of Hematology and Oncology, Department of Medicine, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA; (U.G.); (D.C.)
- Penn State Cancer Institute, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA; (D.T.); (D.D.)
- Department of Pharmacology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
- Correspondence:
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Zhang X, Hong R, Bei L, Yang J, Zhao X, Hu Z, Chen L, Meng H, Zhang Q, Niu G, Yue Y, Ke C. Selenium binding protein 1 inhibits tumor angiogenesis in colorectal cancers by blocking the Delta-like ligand 4/Notch1 signaling pathway. Transl Oncol 2022; 18:101365. [PMID: 35158204 PMCID: PMC8850798 DOI: 10.1016/j.tranon.2022.101365] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2021] [Revised: 01/27/2022] [Accepted: 02/06/2022] [Indexed: 01/03/2023] Open
Abstract
SELENBP1 localizes to vessels and is suppressed in tumor vessels. SELENBP1 inhibits in vivo and in vitro angiogenesis. SELENBP1 antagonizes tumor angiogenesis by blocking the DLL4/Notch1 signaling pathway. SELENBP1 is a candidate target to treat bevacizumab-resistance in colorectal cancer. Background Selenium binding protein 1 (SELENBP1) is frequently downregulated in malignancies such as colorectal cancer (CRC), however, whether it is involved in tumor angiogenesis is still unknown. Methods We analyzed the expression and localization of SELENBP1 in vessels from CRC and neighboring tissues. We investigated the in vitro and in vivo activity of SELENBP1 in angiogenesis and explored the underlying mechanism. Results SELENBP1 was localized to endothelial cells in addition to glandular cells, while its vascular expression was decreased in tumor vessels compared to that in vessels from neighboring non-tumor tissues. Gain-of-function and loss-of-function experiments demonstrated that SELENBP1 inhibited angiogenesis in vitro, and blocked communications between HUVECs and CRC cells. Overexpression of SELENBP1 in CRC cells inhibited tumor growth and angiogenesis, and enhanced bevacizumab-sensitivity in a mouse subcutaneous xenograft model. Mechanic analyses revealed that SELENBP1 may suppress tumor angiogenesis by binding with Delta-like ligand 4 (DLL4) and antagonizing the DLL4/Notch1 signaling pathway. The inhibitory effects of SELENBP1 on in vitro angiogenesis could largely be rescued by DLL4. Conclusion These results revealed a novel role of SELENBP1 as a potential tumor suppressor that antagonizes tumor angiogenesis in CRC by intervening the DLL4/Notch1 signaling pathway.
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Affiliation(s)
- Xiaotian Zhang
- Department of General Surgery, Shanghai Fifth People's Hospital, Fudan University, 801 Heqing Road, Minhang District, Shanghai 200240, China
| | - Runqi Hong
- Department of General Surgery, Shanghai Fifth People's Hospital, Fudan University, 801 Heqing Road, Minhang District, Shanghai 200240, China
| | - Lanxin Bei
- Department of Animal Science, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Ju Yang
- Department of Pathology, Shanghai Fifth People's Hospital, Fudan University, Shanghai 200240, China
| | - Xiaomei Zhao
- Department of Medicine, Dongying New District Hospital, Dongying, Shandong 257000, China
| | - Zhiqing Hu
- Department of General Surgery, Shanghai Fifth People's Hospital, Fudan University, 801 Heqing Road, Minhang District, Shanghai 200240, China
| | - Liang Chen
- Department of General Surgery, Shanghai Fifth People's Hospital, Fudan University, 801 Heqing Road, Minhang District, Shanghai 200240, China
| | - He Meng
- Department of Animal Science, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Qian Zhang
- Department of Orthopedics, The Affiliated Huaihai Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221300, China
| | - Gengming Niu
- Department of General Surgery, Shanghai Fifth People's Hospital, Fudan University, 801 Heqing Road, Minhang District, Shanghai 200240, China.
| | - Ying Yue
- Department of General Surgery, Shanghai Fifth People's Hospital, Fudan University, 801 Heqing Road, Minhang District, Shanghai 200240, China.
| | - Chongwei Ke
- Department of General Surgery, Shanghai Fifth People's Hospital, Fudan University, 801 Heqing Road, Minhang District, Shanghai 200240, China.
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20
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Lin Y, He F, Lian S, Xie B, Liu T, He J, Liu C. Selenium Status in Patients with Chronic Liver Disease: A Systematic Review and Meta-Analysis. Nutrients 2022; 14:nu14050952. [PMID: 35267927 PMCID: PMC8912406 DOI: 10.3390/nu14050952] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Revised: 02/21/2022] [Accepted: 02/22/2022] [Indexed: 02/06/2023] Open
Abstract
Background: The potential role of selenium in preventing chronic liver diseases remains controversial. This meta-analysis aimed to summarize the available evidence from observational studies and intervention trials that had evaluated the associations between body selenium status and chronic liver diseases. Methods: We comprehensively searched MEDLINE, Embase, Web of Science, and Cochrane Library from inception to April 2021. The study protocol was registered at PROSPERO (CRD42020210144). Relative risks (RR) for the highest versus the lowest level of selenium and standard mean differences (SMD) with 95% confidence intervals (CI) were pooled using random-effects models. Heterogeneity and publication bias were evaluated using the I2 statistic and Egger’s regression test, respectively. Results: There were 50 studies with 9875 cases and 12975 population controls in the final analysis. Patients with hepatitis (SMD = −1.78, 95% CI: −2.22 to −1.34), liver cirrhosis (SMD = −2.06, 95% CI: −2.48 to −1.63), and liver cancer (SMD = −2.71, 95% CI: −3.31 to −2.11) had significantly lower selenium levels than controls, whereas there was no significant difference in patients with fatty liver diseases (SMD = 1.06, 95% CI: −1.78 to 3.89). Moreover, the meta-analysis showed that a higher selenium level was significantly associated with a 41% decrease in the incidence of significant advanced chronic liver diseases (RR = 0.59, 95% CI: 0.49 to 0.72). Conclusion: Our meta-analysis suggested that both body selenium status and selenium intake were negatively associated with hepatitis, cirrhosis, and liver cancer. However, the associations for fatty liver diseases were conflicting and need to be established in prospective trials.
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Affiliation(s)
- Yaduan Lin
- Department of Nutrition, School of Medicine, Jinan University, Guangzhou 510632, China; (Y.L.); (S.L.); (B.X.); (T.L.)
| | - Fanchen He
- Institute of Land and Sea Transport Systems, Faculty of Mechanical Engineering and Transport Systems, Technical University of Berlin, 10623 Berlin, Germany;
| | - Shaoyan Lian
- Department of Nutrition, School of Medicine, Jinan University, Guangzhou 510632, China; (Y.L.); (S.L.); (B.X.); (T.L.)
| | - Binbin Xie
- Department of Nutrition, School of Medicine, Jinan University, Guangzhou 510632, China; (Y.L.); (S.L.); (B.X.); (T.L.)
| | - Ting Liu
- Department of Nutrition, School of Medicine, Jinan University, Guangzhou 510632, China; (Y.L.); (S.L.); (B.X.); (T.L.)
| | - Jiang He
- Department of Mathematics and Physics, School of Biomedical Engineering, Southern Medical University, Guangzhou 510515, China
- Correspondence: (J.H.); (C.L.)
| | - Chaoqun Liu
- Department of Nutrition, School of Medicine, Jinan University, Guangzhou 510632, China; (Y.L.); (S.L.); (B.X.); (T.L.)
- Correspondence: (J.H.); (C.L.)
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Mal’tseva VN, Goltyaev MV, Turovsky EA, Varlamova EG. Immunomodulatory and Anti-Inflammatory Properties of Selenium-Containing Agents: Their Role in the Regulation of Defense Mechanisms against COVID-19. Int J Mol Sci 2022; 23:ijms23042360. [PMID: 35216476 PMCID: PMC8880504 DOI: 10.3390/ijms23042360] [Citation(s) in RCA: 36] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Revised: 02/18/2022] [Accepted: 02/19/2022] [Indexed: 02/04/2023] Open
Abstract
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.
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22
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Barchielli G, Capperucci A, Tanini D. The Role of Selenium in Pathologies: An Updated Review. Antioxidants (Basel) 2022; 11:antiox11020251. [PMID: 35204134 PMCID: PMC8868242 DOI: 10.3390/antiox11020251] [Citation(s) in RCA: 161] [Impact Index Per Article: 53.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2021] [Revised: 01/09/2022] [Accepted: 01/25/2022] [Indexed: 12/10/2022] Open
Abstract
Selenium is an essential microelement required for a number of biological functions. Selenium—and more specifically the amino acid selenocysteine—is present in at least 25 human selenoproteins involved in a wide variety of essential biological functions, ranging from the regulation of reactive oxygen species (ROS) concentration to the biosynthesis of hormones. These processes also play a central role in preventing and modulating the clinical outcome of several diseases, including cancer, diabetes, Alzheimer’s disease, mental disorders, cardiovascular disorders, fertility impairments, inflammation, and infections (including SARS-CoV-2). Over the past years, a number of studies focusing on the relationship between selenium and such pathologies have been reported. Generally, an adequate selenium nutritional state—and in some cases selenium supplementation—have been related to improved prognostic outcome and reduced risk of developing several diseases. On the other hand, supra-nutritional levels might have adverse effects. The results of recent studies focusing on these topics are summarized and discussed in this review, with particular emphasis on advances achieved in the last decade.
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Dailey GP, Premadasa LS, Ruzicka JA, Taylor EW. Inhibition of selenoprotein synthesis by Zika virus may contribute to congenital Zika syndrome and microcephaly by mimicking SELENOP knockout and the genetic disease PCCA. BBA ADVANCES 2022; 1. [PMID: 34988542 DOI: 10.1016/j.bbadva.2021.100023] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022] Open
Abstract
Selenium status plays a major role in health impacts of various RNA viruses. We previously reported potential antisense interactions between viral mRNAs and host mRNAs encoding isoforms of the antioxidant selenoprotein thioredoxin reductase (TXNRD). Here, we examine possible targeting of selenoprotein mRNAs by Zika virus (ZIKV), because one of the most devastating outcomes of ZIKV infection in neonates, microcephaly, is a key manifestation of Progressive Cerebello-Cerebral Atrophy (PCCA), a genetic disease of impaired selenoprotein synthesis. Potential antisense matches between ZIKV and human selenoprotein mRNAs were identified computationally, the strongest being against human TXNRD1 and selenoprotein P (SELENOP), a selenium carrier protein essential for delivery of selenium to the brain. Computationally, ZIKV has regions of extensive (~30bp) and stable (ΔE < -50kcal/mol) antisense interactions with both TXNRD1 and SELENOP mRNAs. The core ZIKV/SELENOP hybridization was experimentally confirmed at the DNA level by gel shift assay using synthetic oligonucleotides. In HEK293T cells, using Western blot probes for SELENOP and TXNRD1, ZIKV infection knocked down SELENOP protein expression almost completely, by 99% (p<0.005), and TXNRD1 by ~90% (p<0.05). In contrast, by RT-qPCR, there was no evidence of significant changes in SELENOP and TXNRD1 mRNA levels after ZIKV infection, suggesting that their knockdown at the protein level is not primarily a result of mRNA degradation. These results suggest that knockdown of SELENOP and TXNRD1 by ZIKV in fetal brain, possibly antisense-mediated, could mimic SELENOP knockout, thereby contributing to neuronal cell death and symptoms similar to the genetic disease PCCA, including brain atrophy and microcephaly.
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Affiliation(s)
- Gabrielle P Dailey
- Dept. of Chemistry and Biochemistry, University of North Carolina at Greensboro, 435 Patricia A. Sullivan Science Building, PO Box 26170, Greensboro, NC 27402-6170, United States of America
| | - Lakmini S Premadasa
- Texas Biomedical Research Institute, Southwest National Primate Research Center, P.O. Box 760549, San Antonio, Texas 78245-0549, United States of America
| | - Jan A Ruzicka
- Dept. of Basic Pharmaceutical Sciences, Fred Wilson School of Pharmacy, High Point University, One University Parkway, High Point, NC 27268, United States of America
| | - Ethan Will Taylor
- Dept. of Chemistry and Biochemistry, University of North Carolina at Greensboro, 435 Patricia A. Sullivan Science Building, PO Box 26170, Greensboro, NC 27402-6170, United States of America
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Martinez SS, Huang Y, Acuna L, Laverde E, Trujillo D, Barbieri MA, Tamargo J, Campa A, Baum MK. Role of Selenium in Viral Infections with a Major Focus on SARS-CoV-2. Int J Mol Sci 2021; 23:280. [PMID: 35008706 PMCID: PMC8745607 DOI: 10.3390/ijms23010280] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Revised: 12/22/2021] [Accepted: 12/24/2021] [Indexed: 02/06/2023] Open
Abstract
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.
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Affiliation(s)
- Sabrina Sales Martinez
- Robert Stempel College of Public Health and Social Work, Florida International University, Miami, FL 33199, USA; (S.S.M.); (Y.H.); (J.T.); (A.C.)
| | - Yongjun Huang
- Robert Stempel College of Public Health and Social Work, Florida International University, Miami, FL 33199, USA; (S.S.M.); (Y.H.); (J.T.); (A.C.)
| | - Leonardo Acuna
- College of Arts, Sciences & Education, Florida International University, Miami, FL 33199, USA; (L.A.); (E.L.); (D.T.); (M.A.B.)
| | - Eduardo Laverde
- College of Arts, Sciences & Education, Florida International University, Miami, FL 33199, USA; (L.A.); (E.L.); (D.T.); (M.A.B.)
| | - David Trujillo
- College of Arts, Sciences & Education, Florida International University, Miami, FL 33199, USA; (L.A.); (E.L.); (D.T.); (M.A.B.)
| | - Manuel A. Barbieri
- College of Arts, Sciences & Education, Florida International University, Miami, FL 33199, USA; (L.A.); (E.L.); (D.T.); (M.A.B.)
| | - Javier Tamargo
- Robert Stempel College of Public Health and Social Work, Florida International University, Miami, FL 33199, USA; (S.S.M.); (Y.H.); (J.T.); (A.C.)
| | - Adriana Campa
- Robert Stempel College of Public Health and Social Work, Florida International University, Miami, FL 33199, USA; (S.S.M.); (Y.H.); (J.T.); (A.C.)
| | - Marianna K. Baum
- Robert Stempel College of Public Health and Social Work, Florida International University, Miami, FL 33199, USA; (S.S.M.); (Y.H.); (J.T.); (A.C.)
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Rodríguez-Tomàs E, Baiges-Gaya G, Castañé H, Arenas M, Camps J, Joven J. Trace elements under the spotlight: A powerful nutritional tool in cancer. J Trace Elem Med Biol 2021; 68:126858. [PMID: 34537473 DOI: 10.1016/j.jtemb.2021.126858] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2021] [Revised: 09/01/2021] [Accepted: 09/10/2021] [Indexed: 01/31/2023]
Abstract
Cancer is the second leading cause of death worldwide. Research on the relationships between trace elements (TE) and the development of cancer or its prevention is a field that is gaining increasing relevance. This review provides an evaluation of the effects of TE (As, Al, B, Cd, Cr, Cu, F, I, Pb, Li, Mn, Hg, Mo, Ni, Se, Si, Sn, V and Zn) intake and supplementation in cancer risk and prevention, as well as their interactions with oncology treatments. Advancements in the knowledge of TE, their dietary interactions and their main food sources can provide patients with choices that will help them to improve their quality of life and therapy outcomes. This approach could open new opportunities for treatments based on the integration of conventional therapies (chemotherapy, radiotherapy, and immunotherapy) and dietary interventions that provide advanced personalized treatments.
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Affiliation(s)
- Elisabet Rodríguez-Tomàs
- Unitat de Recerca Biomèdica, Hospital Universitari de Sant Joan, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, C. Sant Joan s/n, 43201, Reus, Spain; Department of Radiation Oncology, Hospital Universitari de Sant Joan, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Av. Doctor Josep Laporte 2, 43204, Reus, Spain
| | - Gerard Baiges-Gaya
- Unitat de Recerca Biomèdica, Hospital Universitari de Sant Joan, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, C. Sant Joan s/n, 43201, Reus, Spain
| | - Helena Castañé
- Unitat de Recerca Biomèdica, Hospital Universitari de Sant Joan, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, C. Sant Joan s/n, 43201, Reus, Spain
| | - Meritxell Arenas
- Unitat de Recerca Biomèdica, Hospital Universitari de Sant Joan, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, C. Sant Joan s/n, 43201, Reus, Spain; Department of Radiation Oncology, Hospital Universitari de Sant Joan, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Av. Doctor Josep Laporte 2, 43204, Reus, Spain
| | - Jordi Camps
- Unitat de Recerca Biomèdica, Hospital Universitari de Sant Joan, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, C. Sant Joan s/n, 43201, Reus, Spain
| | - Jorge Joven
- Unitat de Recerca Biomèdica, Hospital Universitari de Sant Joan, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, C. Sant Joan s/n, 43201, Reus, Spain
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A novel therapeutic strategy for hepatocellular carcinoma: Immunomodulatory mechanisms of selenium and/or selenoproteins on a shift towards anti-cancer. Int Immunopharmacol 2021; 96:107790. [PMID: 34162153 DOI: 10.1016/j.intimp.2021.107790] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Revised: 05/05/2021] [Accepted: 05/13/2021] [Indexed: 12/24/2022]
Abstract
Selenium (Se) is an essential trace chemical element that is widely distributed worldwide. Se exerts its immunomodulatory and nutritional activities in the human body in the form of selenoproteins. Se has increasingly appeared as a potential trace element associated with many human diseases, including hepatocellular carcinoma (HCC). Recently, increasing evidence has suggested that Se and selenoproteins exert their immunomodulatory effects on HCC by regulating the molecules of oxidative stress, inflammation, immune response, cell proliferation and growth, angiogenesis, signaling pathways, apoptosis, and other processes in vitro cell studies and in vivo animal studies. Se concentrations are generally low in tissues of patients with HCC, such as blood, serum, scalp hair, and toenail. However, Se concentrations were higher in HCC patient tissues after Se supplementation than before supplementation. This review summarizes the significant relationship between Se and HCC, and details the role of Se as a novel immunomodulatory or immunotherapeutic approach against HCC.
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Radomska D, Czarnomysy R, Radomski D, Bielawska A, Bielawski K. Selenium as a Bioactive Micronutrient in the Human Diet and Its Cancer Chemopreventive Activity. Nutrients 2021; 13:1649. [PMID: 34068374 PMCID: PMC8153312 DOI: 10.3390/nu13051649] [Citation(s) in RCA: 68] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Revised: 05/06/2021] [Accepted: 05/11/2021] [Indexed: 12/15/2022] Open
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.
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Affiliation(s)
- Dominika Radomska
- Department of Synthesis and Technology of Drugs, Medical University of Bialystok, Kilinskiego 1, 15-089 Bialystok, Poland; (D.R.); (D.R.); (K.B.)
| | - Robert Czarnomysy
- Department of Synthesis and Technology of Drugs, Medical University of Bialystok, Kilinskiego 1, 15-089 Bialystok, Poland; (D.R.); (D.R.); (K.B.)
| | - Dominik Radomski
- Department of Synthesis and Technology of Drugs, Medical University of Bialystok, Kilinskiego 1, 15-089 Bialystok, Poland; (D.R.); (D.R.); (K.B.)
| | - Anna Bielawska
- Department of Biotechnology, Medical University of Bialystok, Kilinskiego 1, 15-089 Bialystok, Poland;
| | - Krzysztof Bielawski
- Department of Synthesis and Technology of Drugs, Medical University of Bialystok, Kilinskiego 1, 15-089 Bialystok, Poland; (D.R.); (D.R.); (K.B.)
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Lv Q, Liang X, Nong K, Gong Z, Qin T, Qin X, Wang D, Zhu Y. Advances in Research on the Toxicological Effects of Selenium. BULLETIN OF ENVIRONMENTAL CONTAMINATION AND TOXICOLOGY 2021; 106:715-726. [PMID: 33420800 DOI: 10.1007/s00128-020-03094-3] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/17/2020] [Accepted: 12/25/2020] [Indexed: 05/28/2023]
Abstract
Selenium is a trace element necessary for the growth of organisms. Moreover, selenium supplementation can improve the immunity and fertility of the body, as well as its ability to resist oxidation, tumors, heavy metals, and pathogenic microorganisms. However, owing to the duality of selenium, excessive selenium supplementation can cause certain toxic effects on the growth and development of the body and may even result in death in severe cases. At present, increasing attention is being paid to the development and utilization of selenium as a micronutrient, but its potential toxicity tends to be neglected. This study systematically reviews recent research on the toxicological effects of selenium, aiming to provide theoretical references for selenium toxicology-related research and theoretical support for the development of selenium-containing drugs, selenium-enriched dietary supplements, and selenium-enriched foods.
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Affiliation(s)
- Qizhuang Lv
- College of Biology & Pharmacy, Yulin Normal University, Yulin, 537000, Guangxi, China
- Guangxi Key Laboratory of Agricultural Resources Chemistry and Biotechnology, Yulin, 537000, Guangxi, China
| | - Xiaomei Liang
- College of Biology & Pharmacy, Yulin Normal University, Yulin, 537000, Guangxi, China
| | - Keyi Nong
- College of Biology & Pharmacy, Yulin Normal University, Yulin, 537000, Guangxi, China
| | - Zifeng Gong
- College of Biology & Pharmacy, Yulin Normal University, Yulin, 537000, Guangxi, China
| | - Ting Qin
- College of Biology & Pharmacy, Yulin Normal University, Yulin, 537000, Guangxi, China
| | - Xinyun Qin
- College of Biology & Pharmacy, Yulin Normal University, Yulin, 537000, Guangxi, China
| | - Daobo Wang
- College of Biology & Pharmacy, Yulin Normal University, Yulin, 537000, Guangxi, China.
| | - Yulin Zhu
- College of Biology & Pharmacy, Yulin Normal University, Yulin, 537000, Guangxi, China.
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29
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Acar O, Izydorczyk M, McMillan T, Yazici M, Ozdemir B, Cakmak I, Koksel H. An investigation on minerals, arabinoxylans and other fibres of biofortified hull-less barley fractions obtained by two milling systems. J Cereal Sci 2020. [DOI: 10.1016/j.jcs.2020.103098] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
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30
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Zhang J, Saad R, Taylor EW, Rayman MP. Selenium and selenoproteins in viral infection with potential relevance to COVID-19. Redox Biol 2020; 37:101715. [PMID: 32992282 PMCID: PMC7481318 DOI: 10.1016/j.redox.2020.101715] [Citation(s) in RCA: 106] [Impact Index Per Article: 21.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2020] [Revised: 09/03/2020] [Accepted: 09/05/2020] [Indexed: 02/07/2023] Open
Abstract
Selenium is a trace element essential to human health largely because of its incorporation into selenoproteins that have a wide range of protective functions. Selenium has an ongoing history of reducing the incidence and severity of various viral infections; for example, a German study found selenium status to be significantly higher in serum samples from surviving than non-surviving COVID-19 patients. Furthermore, a significant, positive, linear association was found between the cure rate of Chinese patients with COVID-19 and regional selenium status. Moreover, the cure rate continued to rise beyond the selenium intake required to optimise selenoproteins, suggesting that selenoproteins are probably not the whole story. Nonetheless, the significantly reduced expression of a number of selenoproteins, including those involved in controlling ER stress, along with increased expression of IL-6 in SARS-CoV-2 infected cells in culture suggests a potential link between reduced selenoprotein expression and COVID-19-associated inflammation. In this comprehensive review, we describe the history of selenium in viral infections and then go on to assess the potential benefits of adequate and even supra-nutritional selenium status. We discuss the indispensable function of the selenoproteins in coordinating a successful immune response and follow by reviewing cytokine excess, a key mediator of morbidity and mortality in COVID-19, and its relationship to selenium status. We comment on the fact that the synthetic redox-active selenium compound, ebselen, has been found experimentally to be a strong inhibitor of the main SARS-CoV-2 protease that enables viral maturation within the host. That finding suggests that redox-active selenium species formed at high selenium intake might hypothetically inhibit SARS-CoV-2 proteases. We consider the tactics that SARS-CoV-2 could employ to evade an adequate host response by interfering with the human selenoprotein system. Recognition of the myriad mechanisms by which selenium might potentially benefit COVID-19 patients provides a rationale for randomised, controlled trials of selenium supplementation in SARS-CoV-2 infection.
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Affiliation(s)
- Jinsong Zhang
- Key Laboratory of Tea Plant Biology and Utilization, School of Tea & Food Science, Anhui Agricultural University, 130 West Changjiang Road, Hefei, 230036, Anhui, PR China
| | - Ramy Saad
- Department of Nutritional Sciences, Faculty of Health and Medical Sciences, University of Surrey, Guildford, GU2 7XH, UK; Royal Sussex County Hospital, Brighton, BN2 5BE, UK
| | - Ethan Will Taylor
- Department of Chemistry and Biochemistry, University of North Carolina Greensboro, Greensboro, NC 27402, USA
| | - Margaret P Rayman
- Department of Nutritional Sciences, Faculty of Health and Medical Sciences, University of Surrey, Guildford, GU2 7XH, UK.
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Acar O, Izydorczyk MS, Kletke J, Atilla Yazici M, Imamoglu A, Cakmak I, Koksel H. Comparison of short and long milling flows on yield and physicochemical properties of brans from biofortified and nonbiofortified hull‐less oats. Cereal Chem 2020. [DOI: 10.1002/cche.10308] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Affiliation(s)
- Oguz Acar
- Department of Food Technology Field Crops Central Research Institute Ankara Turkey
| | - Marta S. Izydorczyk
- Grain Research Laboratory, Canadian Grain Commission Winnipeg Manitoba Canada
| | - Jerry Kletke
- Grain Research Laboratory, Canadian Grain Commission Winnipeg Manitoba Canada
| | - M. Atilla Yazici
- Department of Field Crops, Aegean Agricultural Research Institute Izmir Turkey
| | - Aydin Imamoglu
- Department of Field Crops, Aegean Agricultural Research Institute Izmir Turkey
| | - Ismail Cakmak
- Faculty of Engineering and Natural Sciences Sabanci University Istanbul Turkey
| | - Hamit Koksel
- Department of Food Engineering Hacettepe University Ankara Turkey
- Department of Nutrition and Dietetics Istinye University Istanbul Turkey
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Lee YM, Kim S, Park RY, Kim YS. Hepatitis B Virus-X Downregulates Expression of Selenium Binding Protein 1. Viruses 2020; 12:v12050565. [PMID: 32443734 PMCID: PMC7291177 DOI: 10.3390/v12050565] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2020] [Revised: 05/15/2020] [Accepted: 05/18/2020] [Indexed: 02/06/2023] Open
Abstract
Selenium binding protein 1 (SELENBP1) has been known to be reduced in various types cancer, and epigenetic change is shown to be likely to account for the reduction of SELNEBP1 expression. With cDNA microarray comparative analysis, we found that SELENBP1 is markedly decreased in hepatitis B virus-X (HBx)-expressing cells. To clarify the effect of HBx on SELENBP1 expression, we compared the expression levels of SELENBP1 mRNA and protein by semi-quantitative RT-PCR, Northern blot, and Western blot. As expected, SELENBP1 expression was shown to be reduced in cells expressing HBx, and reporter gene analysis showed that the SELENBP1 promoter is repressed by HBx. In addition, the stepwise deletion of 5′ flanking promoter sequences resulted in a gradual decrease in basal promoter activity and inhibition of SELENBP1 expression by HBx. Moreover, immunohistochemistry on tissue microarrays containing 60 pairs of human liver tissue showed decreased intensity of SELENBP1 in tumor tissues as compared with their matched non-tumor liver tissues. Taken together, our findings suggest that inhibition of SELENBP1 expression by HBx might act as one of the causes in the development of hepatocellular carcinoma caused by HBV infection.
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Affiliation(s)
- Young-Man Lee
- Dasan Undergraduate College, Ajou University, Suwon 16499, Korea;
| | - Soojin Kim
- Graduate School of New Drug Discovery & Development, Chungnam National University, Daejeon 34134, Korea;
| | - Ran-Young Park
- Department of Smart Food & Drugs, Inje University, Gimhae 50834, Korea;
| | - Yeon-Soo Kim
- Graduate School of New Drug Discovery & Development, Chungnam National University, Daejeon 34134, Korea;
- Correspondence: ; Tel.: +82-42-821-8631
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Guillin OM, Vindry C, Ohlmann T, Chavatte L. Selenium, Selenoproteins and Viral Infection. Nutrients 2019; 11:nu11092101. [PMID: 31487871 PMCID: PMC6769590 DOI: 10.3390/nu11092101] [Citation(s) in RCA: 255] [Impact Index Per Article: 42.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2019] [Revised: 08/23/2019] [Accepted: 08/27/2019] [Indexed: 02/07/2023] Open
Abstract
Reactive oxygen species (ROS) are frequently produced during viral infections. Generation of these ROS can be both beneficial and detrimental for many cellular functions. When overwhelming the antioxidant defense system, the excess of ROS induces oxidative stress. Viral infections lead to diseases characterized by a broad spectrum of clinical symptoms, with oxidative stress being one of their hallmarks. In many cases, ROS can, in turn, enhance viral replication leading to an amplification loop. Another important parameter for viral replication and pathogenicity is the nutritional status of the host. Viral infection simultaneously increases the demand for micronutrients and causes their loss, which leads to a deficiency that can be compensated by micronutrient supplementation. Among the nutrients implicated in viral infection, selenium (Se) has an important role in antioxidant defense, redox signaling and redox homeostasis. Most of biological activities of selenium is performed through its incorporation as a rare amino acid selenocysteine in the essential family of selenoproteins. Selenium deficiency, which is the main regulator of selenoprotein expression, has been associated with the pathogenicity of several viruses. In addition, several selenoprotein members, including glutathione peroxidases (GPX), thioredoxin reductases (TXNRD) seemed important in different models of viral replication. Finally, the formal identification of viral selenoproteins in the genome of molluscum contagiosum and fowlpox viruses demonstrated the importance of selenoproteins in viral cycle.
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Affiliation(s)
- Olivia M Guillin
- CIRI, Centre International de Recherche en Infectiologie, CIRI, 69007 Lyon, France
- Institut National de la Santé et de la Recherche Médicale (INSERM) Unité U1111, 69007 Lyon, France
- Ecole Normale Supérieure de Lyon, 69007 Lyon, France
- Université Claude Bernard Lyon 1 (UCBL1), 69622 Lyon, France
- Unité Mixte de Recherche 5308 (UMR5308), Centre national de la recherche scientifique (CNRS), 69007 Lyon, France
| | - Caroline Vindry
- CIRI, Centre International de Recherche en Infectiologie, CIRI, 69007 Lyon, France
- Institut National de la Santé et de la Recherche Médicale (INSERM) Unité U1111, 69007 Lyon, France
- Ecole Normale Supérieure de Lyon, 69007 Lyon, France
- Université Claude Bernard Lyon 1 (UCBL1), 69622 Lyon, France
- Unité Mixte de Recherche 5308 (UMR5308), Centre national de la recherche scientifique (CNRS), 69007 Lyon, France
| | - Théophile Ohlmann
- CIRI, Centre International de Recherche en Infectiologie, CIRI, 69007 Lyon, France
- Institut National de la Santé et de la Recherche Médicale (INSERM) Unité U1111, 69007 Lyon, France
- Ecole Normale Supérieure de Lyon, 69007 Lyon, France
- Université Claude Bernard Lyon 1 (UCBL1), 69622 Lyon, France
- Unité Mixte de Recherche 5308 (UMR5308), Centre national de la recherche scientifique (CNRS), 69007 Lyon, France
| | - Laurent Chavatte
- CIRI, Centre International de Recherche en Infectiologie, CIRI, 69007 Lyon, France.
- Institut National de la Santé et de la Recherche Médicale (INSERM) Unité U1111, 69007 Lyon, France.
- Ecole Normale Supérieure de Lyon, 69007 Lyon, France.
- Université Claude Bernard Lyon 1 (UCBL1), 69622 Lyon, France.
- Unité Mixte de Recherche 5308 (UMR5308), Centre national de la recherche scientifique (CNRS), 69007 Lyon, France.
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Designing selenium functional foods and beverages: A review. Food Res Int 2019; 120:708-725. [DOI: 10.1016/j.foodres.2018.11.029] [Citation(s) in RCA: 48] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2018] [Revised: 10/15/2018] [Accepted: 11/15/2018] [Indexed: 02/07/2023]
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Valueva SV, Borovikova LN. Effect of the Type of Biologically Active Stabilizers on the Spectral and Dimensional Characteristics of Selenium-Containing Hybrid Nanosystems. RUSSIAN JOURNAL OF PHYSICAL CHEMISTRY A 2019. [DOI: 10.1134/s0036024419010308] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
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36
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Valueva SV, Borovikova LN, Kutin AA, Plyushchenko AV. Effect of the Nature of Nanoparticles and Biocompatible Polymer Stabilizers on the Sizes and Spectral Characteristics of Hybrid Nanosystems. RUSSIAN JOURNAL OF PHYSICAL CHEMISTRY A 2019. [DOI: 10.1134/s0036024419020298] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
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Kuria A, Fang X, Li M, Han H, He J, Aaseth JO, Cao Y. Does dietary intake of selenium protect against cancer? A systematic review and meta-analysis of population-based prospective studies. Crit Rev Food Sci Nutr 2018; 60:684-694. [PMID: 30570346 DOI: 10.1080/10408398.2018.1548427] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Current evidence on selenium and its effects on cancer is conflicting. This study aimed at assessing the association between dietary intake of selenium and incidence of cancers by performing systematic review and meta-analysis of population-based prospective studies. We systematically searched for articles in Medline (Ovid), Embase, Web of Science (Thomson Reuters), China National Knowledge Infrastructure, Wanfang Database and VIP Chinese Scientific Journals. Analysis was performed in Stata version 14.2. Of the 2,564 articles obtained from the databases, 39 met our inclusion criteria, 37 were included in the final analysis. Selenium at recommended daily allowance levels of ≥55 μg/day decreased the risk of cancer [relative risk (RR) = 0.94, 95% confidence interval (CI): 0.90-0.98]. A protective effect was found in men at levels ≥55 μg/day (RR = 0.97, 95% CI: 0.94-0.99). Extra selenium intake from supplements was protective at levels ≥55 μg/day (RR = 0.89, 95% CI: 0.82-0.97). There was an inverse relationship (p value = 0.020) between selenium intake and overall cancer risk after adjusting for age, body mass index, and smoking but there was no evidence of nonlinear relationship (p value = 0.261). The findings in this study suggest that selenium is protective against cancer however the effects vary with different cancers.
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Affiliation(s)
- Angelica Kuria
- Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden
| | - Xin Fang
- Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Mei Li
- Center for Assessment of Medical Technology, Örebro University Hospital, Örebro University, Örebro, Sweden
| | - Hedong Han
- Department of Health Statistics, Second Military Medical University, Shanghai, China
| | - Jia He
- Department of Health Statistics, Second Military Medical University, Shanghai, China
| | - Jan Olav Aaseth
- Faculty of Health and Social Sciences, Inland Norway University of Applied Sciences, Elverum, Norway.,Research department, Innlandet Hospital Trust, Brumunddal, Norway
| | - Yang Cao
- Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.,Clinical Epidemiology and Biostatistics, School of Medical Sciences, Örebro University, Örebro, Sweden
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38
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Collery P. Strategies for the development of selenium-based anticancer drugs. J Trace Elem Med Biol 2018; 50:498-507. [PMID: 29548612 DOI: 10.1016/j.jtemb.2018.02.024] [Citation(s) in RCA: 56] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2017] [Revised: 02/20/2018] [Accepted: 02/26/2018] [Indexed: 02/07/2023]
Abstract
Many experimental models demonstrated that inorganic and organic selenium (Se) compounds may have an anticancer activity. However, large clinical studies failed to demonstrate that Se supplementations may prevent the outcome of cancers. Moreover, there are few randomized trials in cancer patients and there is not yet any Se compound recognized as anticancer drug. There is still a need to develop new Se compounds with new strategies. For that, it may be necessary to consider that Se compounds may have a dual role, either as anti-oxidant or as pro-oxidant. Experimental studies demonstrated that it is as pro-oxidant that Se compounds have anticancer effects, even though cancer cells have a pro-oxidant status. The oxidative status differs according to the type of cancer, the stage of the disease and to other parameters. We propose to adapt the doses of the Se compounds to markers of the oxidative stress, but also to markers of angiogenesis, which is strongly related with the oxidative status. A dual role of Se on angiogenesis has also been noted, either as pro-angiogenesis or as anti-angiogenesis. The objective for the development of new Se compounds, having a great selectivity on cancer cells, could be to try to normalize these oxidative and angiogenic markers in cancer patients, with an individual adaptation of doses.
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Affiliation(s)
- Philippe Collery
- Society for the Coordination of Therapeutic Researches, 20220 Algajola, France.
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Sundaram S, Yan L. Dietary Supplementation with Methylseleninic Acid Inhibits Mammary Tumorigenesis and Metastasis in Male MMTV-PyMT Mice. Biol Trace Elem Res 2018; 184:186-195. [PMID: 29032404 DOI: 10.1007/s12011-017-1188-7] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2017] [Accepted: 10/03/2017] [Indexed: 01/04/2023]
Abstract
Male breast cancer, which makes up approximately 1% of all breast cancers, is an aggressive disease with poor prognosis. We investigated the effects of dietary supplementation with selenium in the form of methylseleninic acid [(MSeA) 2.5 mg selenium/kg] on mammary tumorigenesis in male MMTV-PyMT mice. The mammary tumor latency was 14.6 weeks for the MSeA-fed group and 13.8 weeks for the controls fed the AIN93G diet (p < 0.05). Dietary supplementation with MSeA, versus the control, resulted in a 72% reduction in tumor progression, a 46% reduction in both final volume and weight of mammary tumors, and a 70% reduction in the number of lung metastases. Mammary tumorigenesis in MMTV-PyMT mice, versus non-tumor-bearing wild-type mice, resulted in significant increases in concentrations of plasminogen activator inhibitor-1, urokinase plasminogen activator, monocyte chemotactic protein-1, and vascular endothelial growth factor, but not aromatase and estrogen, in the plasma. Concentrations of all variables mentioned above in both plasma and mammary tumors were lower in MSeA-fed mice. Mammary tumorigenesis reduced plasma levels of adiponectin compared to non-tumor-bearing controls. Adiponectin concentrations in mammary tumors, but not in plasma, were higher in MSeA-fed mice than in controls. In summary, dietary supplementation with selenium in the form of MSeA inhibits mammary tumorigenesis and its pulmonary metastasis in male MMTV-PyMT mice.
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Affiliation(s)
- Sneha Sundaram
- U.S. Department of Agriculture, Agricultural Research Service, Grand Forks Human Nutrition Research Center, Grand Forks, ND, 58202, USA
| | - Lin Yan
- U.S. Department of Agriculture, Agricultural Research Service, Grand Forks Human Nutrition Research Center, Grand Forks, ND, 58202, USA.
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Abstract
The relation between the trace element selenium and the etiology of cancer in humans remains elusive and intriguing, despite the number of epidemiologic studies published on the topic. We address some methodologic issues, such as misclassification of exposure, particularly to single selenium compounds, effect modification, confounding, and other sources of bias, which may explain the inconsistencies in the literature. We also review the results of cohort studies, which have yielded either inverse or null or direct associations between selenium exposure and subsequent cancer risk. To date, no beneficial effect on cancer incidence at major sites, including prostate cancer, has emerged from the Finnish program begun in 1984 to increase the average selenium intake in its population. Populations exposed to unusually high or low levels of environmental selenium might offer unique opportunities to investigate if selenium exposure is related to the etiology of human cancer.
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Affiliation(s)
- M Vinceti
- Department of Hygiene, Microbiology & Biostatistics, University of Modena and Reggio Emilia, Modena, Italy
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41
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Shams AZ, Haug U. Strategies for prevention of gastrointestinal cancers in developing countries: a systematic review. J Glob Health 2018; 7:020405. [PMID: 29250323 PMCID: PMC5718709 DOI: 10.7189/jogh.07.020405] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Background Gastrointestinal cancers account for one third of total cancer incidence and mortality in developing countries. To date, there is no systematic synthesis of evidence regarding strategies to prevent gastrointestinal cancers in developing countries. We aimed to provide a systematic overview of studies evaluating strategies for prevention or early detection of the three most common gastrointestinal cancers (gastric, liver and colorectal cancer) in developing countries. Methods We searched MEDLINE, Web of Science and WHO Global Index Medicus databases for relevant articles published until October 2016 using combinations of the search terms “gastrointestinal”, “digestive system”, “gastric”, “liver”, “colorectal”, “cancer”, “prevention”, “early detection” and “developing country” (including names). Results Overall, 73 articles met the inclusion criteria, providing information on short– and long–term outcomes (up to 30 years) from various intervention studies (∼45% randomized). Trials on hepatitis B vaccination consistently showed vaccine efficacy over time and indicated long–term preventive effects on liver cancer incidence that start to become measurable at the population level. Studies on anti–H. pylori treatment suggested a reduction in gastric cancer incidence reaching statistical significance after long–term follow–up, while evidence regarding a preventive effect in persons with precancerous lesions is still inconclusive. The studies regarding colorectal cancer focused on early detection, ∼90% of which were restricted to intermediate endpoints. Conclusion In conclusion, there were a number of studies on gastric and liver cancer prevention in developing countries showing promising results after long–term follow–up. Important next steps include pooled meta–analyses as far as possible given the heterogeneity between studies as well as implementation research.
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Affiliation(s)
- Ahmad Zia Shams
- Epidemiological Cancer Registry Baden-Wuerttemberg, German Cancer Research Centre, Heidelberg, Germany.,Department of Clinical Epidemiology, Leibniz Institute for Prevention Research and Epidemiology, Bremen, Germany
| | - Ulrike Haug
- Department of Clinical Epidemiology, Leibniz Institute for Prevention Research and Epidemiology, Bremen, Germany.,Faculty of Human and Health Sciences, University of Bremen, Bremen, Germany
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Zhang Z, Bi M, Liu Q, Yang J, Xu S. Meta-analysis of the correlation between selenium and incidence of hepatocellular carcinoma. Oncotarget 2018; 7:77110-77116. [PMID: 27780927 PMCID: PMC5363572 DOI: 10.18632/oncotarget.12804] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2016] [Accepted: 10/14/2016] [Indexed: 01/23/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common cancer type. There is a correlation between selenium (Se) deficiency and the incidence of HCC. To clarify the effects of Se level on the risk of HCC patients, a meta-analysis was performed. A total of 9 articles published between 1994 and 2016 worldwide were selected through searching PubMed, EMBASE, web of science, Cochrane Library, Springer Link, Chinese National Knowledge Infrastructure (CNKI), and Chinese Biology Medicine (CBM), and the information were analyzed using a meta-analysis method. Heterogeneity was assessed by using the I2 index. Publication bias was evaluated by Begg's Test analysis. Pooled analysis indicated that patients with HCC had lower Se levels than the healthy controls [standardized mean difference (SMD)= −1.08, 95% confidence intercal (CI) = (−0.136, −0.08), P < 0.001]. Further subgroup analysis showed this effect to be independent of the study design, race or sample collection. In conclusion, this meta-analysis suggested an inverse correlation between Se level and the risk of HCC in humans patients.
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Affiliation(s)
- Ziwei Zhang
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, P. R. China
| | - Mingyu Bi
- Harbin Railway Public Security Bureau Police Dog Base, Harbin 150056, P. R. China
| | - Qi Liu
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, P. R. China
| | - Jie Yang
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, P. R. China
| | - Shiwen Xu
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, P. R. China
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Wang W, Meng FB, Wang ZX, Li X, Zhou DS. Selenocysteine inhibits human osteosarcoma cells growth through triggering mitochondrial dysfunction and ROS-mediated p53 phosphorylation. Cell Biol Int 2018; 42:580-588. [PMID: 29323455 DOI: 10.1002/cbin.10934] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2017] [Accepted: 01/06/2018] [Indexed: 02/06/2023]
Abstract
Osteosarcoma represents the most common primary malignant bone tumor in children and adolescents, which shows severe resistance toward standard chemotherapy because of high invasive capacity and growing incidence. Selenocysteine (SeC) is a naturally available Se-containing amino acid that displays splendid anticancer activities against several human tumors. However, little information about SeC-induced growth inhibition against human osteosarcoma is available. Herein, the anticancer efficiency and underlying mechanism of SeC against human osteosarcoma were evaluated in vitro and in vivo. The results revealed that SeC significantly inhibited MG-63 human osteosarcoma cells growth in vitro through induction of S-phase arrest and apoptosis, as reflected by the decrease of cyclin A and CDK-2, PARP cleavage, and caspases activation. SeC treatment also resulted in mitochondrial dysfunction through affecting Bcl-2 family expression. Moreover, SeC triggered p53 phosphorylation by inducing reactive oxygen species (ROS) overproduction. ROS inhibition effectively blocked SeC-induced cytotoxicity and p53 phosphorylation. Importantly, MG-63 human osteosarcoma xenograft growth in nude mice was significantly suppressed in vivo through triggering apoptosis and p53 phosphorylation. These results indicated that SeC had the potential to inhibit human osteosarcoma cells growth in vitro and in vivo through triggering mitochondrial dysfunction and ROS-mediated p53 phosphorylation, which validated the potential application of Se-containing compounds in treatment of human osteosarcoma.
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Affiliation(s)
- Wei Wang
- Department of Orthopedics, Shandong Provincial Hospital Affiliated to Shandong University, Jingwu Road 324, Jinan, 250021, Shandong, China.,Department of Orthopedics, Linyi People's Hospital Affiliated to Shandong University, Linyi, 276003, Shandong, China
| | - Fan-Bin Meng
- Department of Orthopedics, Linyi People's Hospital Affiliated to Shandong University, Linyi, 276003, Shandong, China
| | - Zhen-Xing Wang
- Department of Orthopedics, Linyi People's Hospital Affiliated to Shandong University, Linyi, 276003, Shandong, China
| | - Xiao Li
- Department of Orthopedics, Linyi People's Hospital Affiliated to Shandong University, Linyi, 276003, Shandong, China
| | - Dong-Sheng Zhou
- Department of Orthopedics, Shandong Provincial Hospital Affiliated to Shandong University, Jingwu Road 324, Jinan, 250021, Shandong, China
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Vinceti M, Filippini T, Del Giovane C, Dennert G, Zwahlen M, Brinkman M, Zeegers MPA, Horneber M, D'Amico R, Crespi CM. Selenium for preventing cancer. Cochrane Database Syst Rev 2018; 1:CD005195. [PMID: 29376219 PMCID: PMC6491296 DOI: 10.1002/14651858.cd005195.pub4] [Citation(s) in RCA: 140] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND This review is the third update of the Cochrane review "Selenium for preventing cancer". Selenium is a naturally occurring element with both nutritional and toxicological properties. Higher selenium exposure and selenium supplements have been suggested to protect against several types of cancer. OBJECTIVES To gather and present evidence needed to address two research questions:1. What is the aetiological relationship between selenium exposure and cancer risk in humans?2. Describe the efficacy of selenium supplementation for cancer prevention in humans. SEARCH METHODS We updated electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 2), MEDLINE (Ovid, 2013 to January 2017, week 4), and Embase (2013 to 2017, week 6), as well as searches of clinical trial registries. SELECTION CRITERIA We included randomised controlled trials (RCTs) and longitudinal observational studies that enrolled adult participants. DATA COLLECTION AND ANALYSIS We performed random-effects (RE) meta-analyses when two or more RCTs were available for a specific outcome. We conducted RE meta-analyses when five or more observational studies were available for a specific outcome. We assessed risk of bias in RCTs and in observational studies using Cochrane's risk assessment tool and the Newcastle-Ottawa Scale, respectively. We considered in the primary analysis data pooled from RCTs with low risk of bias. We assessed the certainty of evidence by using the GRADE approach. MAIN RESULTS We included 83 studies in this updated review: two additional RCTs (10 in total) and a few additional trial reports for previously included studies. RCTs involved 27,232 participants allocated to either selenium supplements or placebo. For analyses of RCTs with low risk of bias, the summary risk ratio (RR) for any cancer incidence was 1.01 (95% confidence interval (CI) 0.93 to 1.10; 3 studies, 19,475 participants; high-certainty evidence). The RR for estimated cancer mortality was 1.02 (95% CI 0.80 to 1.30; 1 study, 17,444 participants). For the most frequently investigated site-specific cancers, investigators provided little evidence of any effect of selenium supplementation. Two RCTs with 19,009 participants indicated that colorectal cancer was unaffected by selenium administration (RR 0.99, 95% CI 0.69 to 1.43), as were non-melanoma skin cancer (RR 1.16, 95% CI 0.30 to 4.42; 2 studies, 2027 participants), lung cancer (RR 1.16, 95% CI 0.89 to 1.50; 2 studies, 19,009 participants), breast cancer (RR 2.04, 95% CI 0.44 to 9.55; 1 study, 802 participants), bladder cancer (RR 1.07, 95% CI 0.76 to 1.52; 2 studies, 19,009 participants), and prostate cancer (RR 1.01, 95% CI 0.90 to 1.14; 4 studies, 18,942 participants). Certainty of the evidence was high for all of these cancer sites, except for breast cancer, which was of moderate certainty owing to imprecision, and non-melanoma skin cancer, which we judged as moderate certainty owing to high heterogeneity. RCTs with low risk of bias suggested increased melanoma risk.Results for most outcomes were similar when we included all RCTs in the meta-analysis, regardless of risk of bias. Selenium supplementation did not reduce overall cancer incidence (RR 0.99, 95% CI 0.86 to 1.14; 5 studies, 21,860 participants) nor mortality (RR 0.81, 95% CI 0.49 to 1.32; 2 studies, 18,698 participants). Summary RRs for site-specific cancers showed limited changes compared with estimates from high-quality studies alone, except for liver cancer, for which results were reversed.In the largest trial, the Selenium and Vitamin E Cancer Trial, selenium supplementation increased risks of alopecia and dermatitis, and for participants with highest background selenium status, supplementation also increased risk of high-grade prostate cancer. RCTs showed a slightly increased risk of type 2 diabetes associated with supplementation. A hypothesis generated by the Nutritional Prevention of Cancer Trial - that individuals with low blood selenium levels could reduce their risk of cancer (particularly prostate cancer) by increasing selenium intake - has not been confirmed. As RCT participants have been overwhelmingly male (88%), we could not assess the potential influence of sex or gender.We included 15 additional observational cohort studies (70 in total; over 2,360,000 participants). We found that lower cancer incidence (summary odds ratio (OR) 0.72, 95% CI 0.55 to 0.93; 7 studies, 76,239 participants) and lower cancer mortality (OR 0.76, 95% CI 0.59 to 0.97; 7 studies, 183,863 participants) were associated with the highest category of selenium exposure compared with the lowest. Cancer incidence was lower in men (OR 0.72, 95% CI 0.46 to 1.14, 4 studies, 29,365 men) than in women (OR 0.90, 95% CI 0.45 to 1.77, 2 studies, 18,244 women). Data show a decrease in risk of site-specific cancers for stomach, colorectal, lung, breast, bladder, and prostate cancers. However, these studies have major weaknesses due to study design, exposure misclassification, and potential unmeasured confounding due to lifestyle or nutritional factors covarying with selenium exposure beyond those taken into account in multi-variable analyses. In addition, no evidence of a dose-response relation between selenium status and cancer risk emerged. Certainty of evidence was very low for each outcome. Some studies suggested that genetic factors might modify the relation between selenium and cancer risk - an issue that merits further investigation. AUTHORS' CONCLUSIONS Well-designed and well-conducted RCTs have shown no beneficial effect of selenium supplements in reducing cancer risk (high certainty of evidence). Some RCTs have raised concerns by reporting a higher incidence of high-grade prostate cancer and type 2 diabetes in participants with selenium supplementation. No clear evidence of an influence of baseline participant selenium status on outcomes has emerged in these studies.Observational longitudinal studies have shown an inverse association between selenium exposure and risk of some cancer types, but null and direct relations have also been reported, and no systematic pattern suggesting dose-response relations has emerged. These studies suffer from limitations inherent to the observational design, including exposure misclassification and unmeasured confounding.Overall, there is no evidence to suggest that increasing selenium intake through diet or supplementation prevents cancer in humans. However, more research is needed to assess whether selenium may modify the risk of cancer in individuals with a specific genetic background or nutritional status, and to investigate possible differential effects of various forms of selenium.
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Affiliation(s)
- Marco Vinceti
- Boston University School of Public HealthDepartment of Epidemiology715 Albany StreetBoston, MAUSA02118
- University of Modena and Reggio EmiliaResearch Center in Environmental, Nutritional and Genetic Epidemiology (CREAGEN), Department of Biomedical, Metabolic and Neural SciencesVia Campi 287ModenaItaly41125
| | - Tommaso Filippini
- University of Modena and Reggio EmiliaResearch Center in Environmental, Nutritional and Genetic Epidemiology (CREAGEN), Department of Biomedical, Metabolic and Neural SciencesVia Campi 287ModenaItaly41125
| | - Cinzia Del Giovane
- University of BernInstitute of Primary Health Care (BIHAM)Gesellschaftsstrasse 49BernSwitzerland3012
- University of Modena and Reggio EmiliaCochrane Italy, Department of Diagnostic, Clinical and Public Health MedicineVia del Pozzo, 71ModenaItaly41100
| | - Gabriele Dennert
- University of Applied Sciences DortmundSocial Medicine and Public Health with Focus on Gender and Diversity, Department of Applied Social SciencesEmil‐Figge‐Str. 44DortmundGermanyD‐44227
| | - Marcel Zwahlen
- University of BernInstitute of Social and Preventive Medicine (ISPM)Finkelhubelweg11BernSwitzerland3012
| | - Maree Brinkman
- Nutrition Biomed Research InstituteDepartment of Nutritional Epidemiology and Clinical StudiesArgyle Place SouthMelbourneVictoriaAustralia3053
- Chairgroup of Complex Genetics and Epidemiology, School for Nutrition and Translational Research in Metabolism, Care and Public Health Research InstituteUnit of Nutritional and Cancer EpidemiologyMaastricht UniversityMaastrichtNetherlands
| | | | - Markus Horneber
- Paracelsus Medical University, Klinikum NurembergDepartment of Internal Medicine, Division of Oncology and HematologyProf.‐Ernst‐Nathan‐Str. 1NurembergGermanyD‐90419
| | - Roberto D'Amico
- University of Modena and Reggio EmiliaCochrane Italy, Department of Diagnostic, Clinical and Public Health MedicineVia del Pozzo, 71ModenaItaly41100
| | - Catherine M Crespi
- University of California Los AngelesBiostatisticsFielding School of Public Health650 Charles Young Drive South, A2‐125 CHS, Box 956900Los AngelesCaliforniaUSA90095‐6900
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Impact of glutathione peroxidase 4 on cell proliferation, angiogenesis and cytokine production in hepatocellular carcinoma. Oncotarget 2018. [PMID: 29515790 PMCID: PMC5839371 DOI: 10.18632/oncotarget.24300] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023] Open
Abstract
Insufficient supplementation with the micronutrient selenium and persistent hepatic inflammation predispose to hepatocellular carcinoma (HCC). Inflammation-associated reactive oxygen species attack membrane lipids and form lipid hydroperoxides able to propagate oxidative hepatic damage. Selenium-containing enzyme glutathione peroxidase 4 (GPx4) antagonizes this damage by reducing lipid hydroperoxides to respective hydroxides. However, the role of GPx4 in HCC remains elusive. We generated two human HCC cell lines with stable overexpression of GPx4, performed xenotransplantation into NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) host mice and characterized the tumors formed. The experimental data were verified using gene expression data from two independent HCC patient cohorts. GPx4 overexpression protected from oxidative stress and reduced intracellular free radical level. GPx4-overexpressing cells displayed impaired tumor growth, reduced proliferation, altered angiogenesis and decreased expression of clinically relevant cytokine interleukin-8 and C-reactive protein. Moreover, GPx4 overexpression impaired migration of endothelial cells in vitro, and enhanced expression of thrombospondin 1, an endogenous inhibitor of angiogenesis. In patients, GPx4 expression in tumors positively correlated with survival and was linked to pathways which regulate cell proliferation, motility, tissue remodelling, immune response and M1 macrophage polarization. The patient data largely confirmed experimental findings especially in a subclass of poor prognosis tumors with high proliferation. GPx4 suppresses formation and progression of HCC by inhibition of angiogenesis and tumor cell proliferation as well as by immune-mediated mechanisms. Modification of GPx4 expression may represent a novel tool for HCC prevention or treatment.
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St. John TM. Chronic Hepatitis. Integr Med (Encinitas) 2018. [DOI: 10.1016/b978-0-323-35868-2.00021-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Abstract
The relation between selenium and cancer has been one of the most hotly debated topics in human health over the last decades. Early observational studies reported an inverse relation between selenium exposure and cancer risk. Subsequently, randomized controlled trials showed that selenium supplementation does not reduce the risk of cancer and may even increase it for some types, including advanced prostate cancer and skin cancer. An increased risk of diabetes has also been reported. These findings have been consistent in the most methodologically sound trials, suggesting that the early observational studies were misleading. Other studies have investigated selenium compounds as adjuvant therapy for cancer. Though there is currently insufficient evidence regarding the utility and safety of selenium compounds for such treatments, this issue is worthy of further investigation. The study of selenium and cancer is complicated by the existence of a diverse array of organic and inorganic selenium compounds, each with distinct biological properties, and this must be taken into consideration in the interpretation of both observational and experimental human studies.
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Affiliation(s)
- Marco Vinceti
- Environmental, Genetic and Nutritional Epidemiology Research Center (CREAGEN), University of Modena and Reggio Emilia, Modena, Italy; Boston University School of Public Health, Boston, MA, United States.
| | - Tommaso Filippini
- Environmental, Genetic and Nutritional Epidemiology Research Center (CREAGEN), University of Modena and Reggio Emilia, Modena, Italy
| | - Silvia Cilloni
- Environmental, Genetic and Nutritional Epidemiology Research Center (CREAGEN), University of Modena and Reggio Emilia, Modena, Italy
| | - Catherine M Crespi
- Jonsson Comprehensive Cancer Center, UCLA Fielding School of Public Health, University of California, Los Angeles, CA, United States
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Sandsveden M, Manjer J. Selenium and breast cancer risk: A prospective nested case-control study on serum selenium levels, smoking habits and overweight. Int J Cancer 2017; 141:1741-1750. [PMID: 28681438 DOI: 10.1002/ijc.30875] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2017] [Revised: 06/15/2017] [Accepted: 06/21/2017] [Indexed: 01/20/2023]
Abstract
Previous research has not been conclusive regarding the association between selenium (Se) and breast cancer. This study was conducted to clarify if there is an association between prediagnostic serum Se levels and breast cancer risk. A population based cohort, the Malmö Diet and Cancer Study, was used and linked with the Swedish cancer registry up to 31 December 2013. Our study included 1,186 women with breast cancer and an equal number of controls. Selenium levels were analysed from stored serum samples. The included individuals were divided into quartiles based on Se value and we compared breast cancer cases with controls using logistic regression yielding odds ratios (OR) with 95% confidence intervals. Serum Se was also analysed as a continuous variable regarding breast cancer risk. The analyses were adjusted for established risk factors and stratified on smoking status and body mass index (BMI). When comparing the highest Se quartile with the lowest, the adjusted OR for breast cancer was 0.98 (0.75-1.26). With selenium as a continuous variable the adjusted OR was 1.00 (1.00-1.01) per 10 ng/ml. When comparing the highest with the lowest Se quartile in women with BMI > 25 kg/m2 the adjusted OR was 0.77 (0.53-1.14). We conclude that it is unlikely that prediagnostic serum selenium is overall associated with breast cancer risk and no modifying effect from BMI or smoking was seen.
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Affiliation(s)
- Malte Sandsveden
- Department of Surgery, Skåne University Hospital Malmö, Lund University, Malmö, Sweden
| | - Jonas Manjer
- Department of Surgery, Skåne University Hospital Malmö, Lund University, Malmö, Sweden
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Ivory K, Nicoletti C. Selenium is a source of aliment and ailment: Do we need more? Trends Food Sci Technol 2017. [DOI: 10.1016/j.tifs.2016.11.012] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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Vinceti M, Filippini T, Cilloni S, Bargellini A, Vergoni AV, Tsatsakis A, Ferrante M. Health risk assessment of environmental selenium: Emerging evidence and challenges (Review). Mol Med Rep 2017; 15:3323-3335. [PMID: 28339083 PMCID: PMC5428396 DOI: 10.3892/mmr.2017.6377] [Citation(s) in RCA: 94] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2017] [Accepted: 02/20/2017] [Indexed: 12/22/2022] Open
Abstract
New data have been accumulated in the scientific literature in recent years which allow a more adequate risk assessment of selenium with reference to human health. This new evidence comes from environmental studies, carried out in populations characterized by abnormally high or low selenium intakes, and from high-quality and large randomized controlled trials with selenium recently carried out in the US and in other countries. These trials have consistently shown no beneficial effect on cancer and cardiovascular risk, and have yielded indications of unexpected toxic effects of selenium exposure. Overall, these studies indicate that the minimal amount of environmental selenium which is source of risk to human health is much lower than anticipated on the basis of older studies, since toxic effects were shown at levels of intake as low as around 260 µg/day for organic selenium and around 16 µg/day for inorganic selenium. Conversely, populations with average selenium intake of less than 13–19 µg/day appear to be at risk of a severe cardiomyopathy, Keshan disease. Overall, there is the need to reconsider the selenium standards for dietary intake, drinking water, outdoor and indoor air levels, taking into account the recently discovered adverse health effects of low-dose selenium overexposure, and carefully assessing the significance of selenium-induced proteomic changes.
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Affiliation(s)
- Marco Vinceti
- CREAGEN, Research Center of Environmental, Genetic and Nutritional Epidemiology, Section of Public Health, University of Modena and Reggio Emilia, Modena, Italy
| | - Tommaso Filippini
- CREAGEN, Research Center of Environmental, Genetic and Nutritional Epidemiology, Section of Public Health, University of Modena and Reggio Emilia, Modena, Italy
| | - Silvia Cilloni
- CREAGEN, Research Center of Environmental, Genetic and Nutritional Epidemiology, Section of Public Health, University of Modena and Reggio Emilia, Modena, Italy
| | - Annalisa Bargellini
- CREAGEN, Research Center of Environmental, Genetic and Nutritional Epidemiology, Section of Public Health, University of Modena and Reggio Emilia, Modena, Italy
| | - Anna Valeria Vergoni
- Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy
| | - Aristides Tsatsakis
- Department of Forensic Sciences and Toxicology, University of Crete, Heraklion, Crete, Greece
| | - Margherita Ferrante
- Department of Medical, Surgical Sciences and Advanced Technologies 'G.F. Ingrassia', University of Catania, Catania, Italy
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