A novel therapeutic strategy for hepatocellular carcinoma: Immunomodulatory mechanisms of selenium and/or selenoproteins on a shift towards anti-cancer

Wu, Baokang; Chen, Qian-Hui; Pan, Dan; Chang, Bing; Sang, Li-Xuan

doi:10.1016/j.intimp.2021.107790

Cited by 17 publications

(6 citation statements)

References 248 publications

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“…The biological function of Se, as an essential micronutrient, is principally regulated by the synthesis of selenoproteins [ 3 , 33 ]. So far, 25 genes coding for selenocysteine-containing proteins have been identified in humans, and some of these proteins are involved in tumorigenesis [ 34 , 35 ]. To evaluate the potential connections between ZIP8 expression and the selenocysteine-containing proteins in cancers, we obtained and summarized the co-expression data of ZIP8 and selenoprotein genes in a range of cancer types from TCGA database ( Figure 7 ).…”

Section: Resultsmentioning

confidence: 99%

The Impact of ZIP8 Disease-Associated Variants G38R, C113S, G204C, and S335T on Selenium and Cadmium Accumulations: The First Characterization

Liang

Tan

et al. 2021

IJMS

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The metal cation symporter ZIP8 (SLC39A8) is a transmembrane protein that imports the essential micronutrients iron, manganese, and zinc, as well as heavy toxic metal cadmium (Cd). It has been recently suggested that selenium (Se), another essential micronutrient that has long been known for its role in human health and cancer risk, may also be transported by the ZIP8 protein. Several mutations in the ZIP8 gene are associated with the aberrant ion homeostasis of cells and can lead to human diseases. However, the intricate relationships between ZIP8 mutations, cellular Se homeostasis, and human diseases (including cancers and illnesses associated with Cd exposure) have not been explored. To further verify if ZIP8 is involved in cellular Se transportation, we first knockout (KO) the endogenous expression of ZIP8 in the HeLa cells using the CRISPR/Cas9 system. The elimination of ZIP8 expression was examined by PCR, DNA sequencing, immunoblot, and immunofluorescence analyses. Inductively coupled plasma mass spectrometry indicated that reduced uptake of Se, along with other micronutrients and Cd, was observed in the ZIP8-KO cells. In contrast, when ZIP8 was overexpressed, increased Se uptake could be detected in the ZIP8-overexpressing cells. Additionally, we found that ZIP8 with disease-associated single-point mutations G38R, G204C, and S335T, but not C113S, showed reduced Se transport ability. We then evaluated the potential of Se on Cd cytotoxicity prevention and therapy of cancers. Results indicated that Se could suppress Cd-induced cytotoxicity via decreasing the intracellular Cd transported by ZIP8, and Se exhibited excellent anticancer activity against not all but only selected cancer cell lines, under restricted experimental conditions. Moreover, clinical-based bioinformatic analyses revealed that up-regulated ZIP8 gene expression was common across multiple cancer types, and selenoproteins that were significantly co-expressed with ZIP8 in these cancers had been identified. Taken together, this study concludes that ZIP8 is an important protein in modulating cellular Se levels and provides insights into the roles of ZIP8 and Se in disease prevention and therapy.

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Section: Resultsmentioning

confidence: 99%

The Impact of ZIP8 Disease-Associated Variants G38R, C113S, G204C, and S335T on Selenium and Cadmium Accumulations: The First Characterization

Liang

Tan

et al. 2021

IJMS

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“…Scientists indicate that selenium exhibits anti-inflammatory effects and inhibits the proliferation of cancer cells in the case of HCC. It directs them towards apoptotic pathways, making it a supportive microelement in therapy [ 73 ]. Dietary supplementation to address selenium deficiencies appears to be the most favorable method due to its toxic effects resulting from excessively high doses [ 74 ].…”

Section: Vitamins and Trace Elements As Supportive Elements In The Pr...mentioning

confidence: 99%

The Influence of Diet and Its Components on the Development and Prevention of Hepatocellular Carcinoma (HCC)

Janota,

Szymanek

2024

Cancers

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Hepatocellular carcinoma (HCC) is diagnosed annually in nearly a million people worldwide, with approximately half of them being diagnosed at an advanced stage of the disease. Non-infectious risk factors for the development of HCC include an unbalanced lifestyle, including poor dietary choices characterized by a low intake of antioxidants, such as vitamins E and C, selenium, and polyphenols, as well as an excessive consumption of energy and harmful substances. Repeated bad dietary choices that contribute to an unbalanced lifestyle lead to the accumulation of fatty substances in the liver and to it entering an inflammatory state, which, without intervention, results in cirrhosis, the main cause of HCC. This review of the English language literature aims to present the food components that, when included in the daily diet, reduce the risk of developing HCC, as well as identifying foods that may have a carcinogenic effect on liver cells.

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“…In this situation, redox imbalance is induced by regulating selenoproteins at mRNA and protein levels by blocking the GSH system while enhancing GSH synthesis and catabolism [137]. In hepatocellular carcinoma, selenium plays an immunomodulatory role by regulating oxidative stress, inflammation, immune response, cell proliferation and growth, angiogenesis, signaling pathways, and apoptosis [136,138]. As shown by Sang et al, Se concentration was usually low in patients with hepatocellular carcinoma, and enhancing the Se concentration via exogenous supplementation was correlated with reducing the number and size of tumors [138].…”

Section: Implications Of Selenoproteins In Liver Diseasesmentioning

confidence: 99%

“Alphabet” Selenoproteins: Implications in Pathology

Dogaru,

Duță,

Muscurel

et al. 2023

IJMS

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Selenoproteins are a group of proteins containing selenium in the form of selenocysteine (Sec, U) as the 21st amino acid coded in the genetic code. Their synthesis depends on dietary selenium uptake and a common set of cofactors. Selenoproteins accomplish diverse roles in the body and cell processes by acting, for example, as antioxidants, modulators of the immune function, and detoxification agents for heavy metals, other xenobiotics, and key compounds in thyroid hormone metabolism. Although the functions of all this protein family are still unknown, several disorders in their structure, activity, or expression have been described by researchers. They concluded that selenium or cofactors deficiency, on the one hand, or the polymorphism in selenoproteins genes and synthesis, on the other hand, are involved in a large variety of pathological conditions, including type 2 diabetes, cardiovascular, muscular, oncological, hepatic, endocrine, immuno-inflammatory, and neurodegenerative diseases. This review focuses on the specific roles of selenoproteins named after letters of the alphabet in medicine, which are less known than the rest, regarding their implications in the pathological processes of several prevalent diseases and disease prevention.

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A novel therapeutic strategy for hepatocellular carcinoma: Immunomodulatory mechanisms of selenium and/or selenoproteins on a shift towards anti-cancer

Cited by 17 publications

References 248 publications

The Impact of ZIP8 Disease-Associated Variants G38R, C113S, G204C, and S335T on Selenium and Cadmium Accumulations: The First Characterization

The Impact of ZIP8 Disease-Associated Variants G38R, C113S, G204C, and S335T on Selenium and Cadmium Accumulations: The First Characterization

The Influence of Diet and Its Components on the Development and Prevention of Hepatocellular Carcinoma (HCC)

“Alphabet” Selenoproteins: Implications in Pathology

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