Methylseleninic acid inhibits HDAC activity in diffuse large B-cell lymphoma cell lines

Kassam, Shireen; Goenaga‐Infante, Heidi; Maharaj, Lenushka; Hiley, Crispin; Jüliger, Simone; Joel, Simon P.

doi:10.1007/s00280-011-1649-1

Cited by 37 publications

(40 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Additionally, a continuous generation of CH 3 SeH might be of importance for successful modulation of NKG2D ligands in vivo to counteract the naturally occurring metabolism of CH 3 SeH into dimethylselenide, trimethylselenonium, or H 2 Se. Notably, the tested Jurkat T cell line, but also other lymphoma cell lines, can generate the volatile selenium metabolites CH 3 SeH, DMDSe, and dimethylselenide in vitro because of the presence of the required and functional enzymes (26,68,80). When taken up by cells, MSA can also be reduced to CH 3 SeH via a nonenzymatic process (81).…”

Section: Discussionmentioning

confidence: 99%

The Selenium Metabolite Methylselenol Regulates the Expression of Ligands That Trigger Immune Activation through the Lymphocyte Receptor NKG2D

Hagemann-Jensen

Uhlenbrock

Kehlet

et al. 2014

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: Immune activation through a balanced cell surface expression of human NKG2D ligands is crucial for the elimination of diseased cells. Results: Methylselenol induces the expression of the NKG2D ligands MICA/B but specifically inhibits ULBP2 protein expression. Conclusion: Methylselenol regulates NKG2D ligand expression on transcriptional and posttranscriptional levels. Significance: Methylselenol is the first identified metabolite that diversely regulates NKG2D ligands, and, therefore, its implementation could improve NKG2D-based immune therapy.

show abstract

Section: Discussionmentioning

confidence: 99%

The Selenium Metabolite Methylselenol Regulates the Expression of Ligands That Trigger Immune Activation through the Lymphocyte Receptor NKG2D

Hagemann-Jensen

Uhlenbrock

Kehlet

et al. 2014

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…For example, both selenite and Se-Met may be metabolized into methylated Se compounds, some of which have cancer chemopreventive effects (113). One example is the inhibition histone deacetylase (HDAC) activity in diffuse large B-cell lymphoma cell lines by methylseleninic acid and the toxic effects this may exert in chemoprevention (125). In addition, some studies have used the selenoorganic compound, ebselen, to show that macrophage and dendritic cell functions are affected by this smallmolecular-weight selenocompound (156,229).…”

Section: Bioactive Forms Of Se and Their Effectsmentioning

confidence: 99%

“…FoxP3, forkhead box P3; RANKL, receptor activator for nuclear factor-jB ligand. been shown to be inhibiited by the small organic selenocompound, methylseleninic acid (125). Chronic inflammation may be an underlying risk factor in the early stages of cancer development, as well as being a key feature of inflammatory bowel disease (IBD).…”

Section: Fig 11 Analyses Of Cell Markers During Activation Of Naivementioning

confidence: 99%

The Role of Selenium in Inflammation and Immunity: From Molecular Mechanisms to Therapeutic Opportunities

Huang

Rose

Hoffmann

2012

Antioxidants & Redox Signaling

682

496

View full text Add to dashboard Cite

Dietary selenium (]Se), mainly through its incorporation into selenoproteins, plays an important role in inflammation and immunity. Adequate levels of Se are important for initiating immunity, but they are also involved in regulating excessive immune responses and chronic inflammation. Evidence has emerged regarding roles for individual selenoproteins in regulating inflammation and immunity, and this has provided important insight into mechanisms by which Se influences these processes. Se deficiency has long been recognized to negatively impact immune cells during activation, differentiation, and proliferation. This is related to increased oxidative stress, but additional functions such as protein folding and calcium flux may also be impaired in immune cells under Se deficient conditions. Supplementing diets with above-adequate levels of Se can also impinge on immune cell function, with some types of inflammation and immunity particularly affected and sexually dimorphic effects of Se levels in some cases. In this comprehensivearticle, the roles of Se and individual selenoproteins in regulating immune cell signaling and function are discussed. Particular emphasis is given to how Se and selenoproteins are linked to redox signaling, oxidative burst, calcium flux, and the subsequent effector functions of immune cells. Data obtained from cell culture and animal models are reviewed and compared with those involving human physiology and pathophysiology, including the effects of Se levels on inflammatory or immune-related diseases including anti-viral immunity, autoimmunity, sepsis, allergic asthma, and chronic inflammatory disorders. Finally, the benefits and potential adverse effects of intervention with Se supplementation for various inflammatory or immune disorders are discussed. Antioxid. Redox Signal. 16, 705-743.

show abstract

“…One explanation might be that MSA has been suggested to inhibit HDACs. 20 In line with this hypothesis, HDAC inhibitors have been described to upregulate both MHC class I and class II molecules at the cell surface. 60 In addition, MSA has been shown to induce the expression of MICA and MICB in Jurkat cells to the same extent as HDAC inhibitors.…”

Section: Discussionmentioning

confidence: 80%

“…HDACs are involved in the regulation of the gene expression pattern and often overexpressed in tumor cells. In B cell lymphoma and esophageal cancer, MSA reduces HDAC activity 19,20 by modulation of conserved cysteine residues in the catalytic center of HDACs. 21 Different models of tumor-initiation showed that natural killer (NK) cells and the interferon (IFN) system are involved in the immunity of tumors.…”

Section: Introductionmentioning

confidence: 99%

Modulation of MHC class I surface expression in B16F10 melanoma cells by methylseleninic acid

et al. 2017

View full text Add to dashboard Cite

The essential trace element selenium (Se) might play a role in cancer prevention as well as for cancer therapy. Its metabolite methylselenol is able to kill cells through distinct mechanisms including induction of reactive oxygen species, DNA damage and apoptosis. Since methylselenol affects innate immune responses by modulating the expression of NKG2D ligands, the aim of this study was to determine whether the methylselenol generating compound methylseleninic acid (MSA) influences the expression of the MHC class I surface antigens and growth properties thereby reverting immune escape.Treatment of B16F10 melanoma cells expressing low basal MHC class I surface antigens with dimethyldiselenide (DMDSe) and MSA, but not with selenomethionine and selenite resulted in a dosedependent upregulation of MHC class I cell surface antigens. This was due to a transcriptional upregulation of some major components of the antigen processing machinery (APM) and the interferon (IFN) signaling pathway and accompanied by a reduced migration of B16F10 melanoma cells in the presence of MSA. Comparative "ome"-based profilings of untreated and MSA-treated melanoma cells linked the anti-oxidative response system with MHC class I antigen processing. Since MSA treatment enhanced MHC class I surface expression also on different human tumors cell lines, MSA might affect the malignant phenotype of various tumor cells by restoring MHC class I APM component expression due to an altered redox status and by partially mimicking IFN-gamma signaling thereby providing a novel mechanism for the chemotherapeutic potential of methylselenol generating Se compounds.

show abstract

Methylseleninic acid inhibits HDAC activity in diffuse large B-cell lymphoma cell lines

Cited by 37 publications

References 26 publications

The Selenium Metabolite Methylselenol Regulates the Expression of Ligands That Trigger Immune Activation through the Lymphocyte Receptor NKG2D

The Selenium Metabolite Methylselenol Regulates the Expression of Ligands That Trigger Immune Activation through the Lymphocyte Receptor NKG2D

The Role of Selenium in Inflammation and Immunity: From Molecular Mechanisms to Therapeutic Opportunities

Modulation of MHC class I surface expression in B16F10 melanoma cells by methylseleninic acid

Contact Info

Product

Resources

About