ArticleCarcinogenesis2009
Alpha-keto acid metabolites of organoselenium compounds inhibit histone deacetylase activity in human colon cancer cells.
Article in Carcinogenesis, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 77 citations in OpenAlex.
- Selenium-enriched foods are more effective at increasing glutathione peroxidase (GPx) activity compared with selenomethionine: a meta-analysis.Nutrients · 2014Pooled it
- Structural and functional modulation of human kynurenine aminotransferase I enhances selenium-driven redox metabolism for cancer therapy.Redox biology · 2026Article
- Epigenetic Histone Deacetylases Activity Assay in the Brain and Peripheral Organ Tissues.Current protocols · 2025Article
- The Histone Deacetylase Family: Structural Features and Application of Combined Computational Methods.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Targeting SMAD-Dependent Signaling: Considerations in Epithelial and Mesenchymal Solid Tumors.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Preparative Biocatalytic Synthesis of α-Ketomethylselenobutyrate-A Putative Agent for Cancer Therapy.Molecules (Basel, Switzerland) · 2023Article
- BRD9 Inhibition by Natural Polyphenols Targets DNA Damage/Repair and Apoptosis in Human Colon Cancer Cells.Nutrients · 2022Article
- The Effect of Organoselenium Compounds on Histone Deacetylase Inhibition and Their Potential for Cancer Therapy.International journal of molecular sciences · 2021Review
- The Effect of Methylselenocysteine and Sodium Selenite Treatment on microRNA Expression in Liver Cancer Cell Lines.Pathology oncology research : POR · 2020Article
- A Novel Assay Method to Determine the β-Elimination of Se-Methylselenocysteine to Monomethylselenol by Kynurenine Aminotransferase 1.Antioxidants (Basel, Switzerland) · 2020Article
- High Levels of Glutaminase II Pathway Enzymes in Normal and Cancerous Prostate Suggest a Role in 'Glutamine Addiction'.Biomolecules · 2019Article
- Measuring Histone Deacetylase Inhibition in the Brain.Current protocols in pharmacology · 2018Article
- Effect of dietary components on miRNA and colorectal carcinogenesis.Cancer cell international · 2018Review
- Anticancer Natural Compounds as Epigenetic Modulators of Gene Expression.Current genomics · 2017Review
- Kynurenine aminotransferase 3/glutamine transaminase L/cysteine conjugate beta-lyase 2 is a major glutamine transaminase in the mouse kidney.Biochemistry and biophysics reports · 2016Article
- Reciprocal regulation of BMF and BIRC5 (Survivin) linked to Eomes overexpression in colorectal cancer.Cancer letters · 2016Article
- Histone and Non-Histone Targets of Dietary Deacetylase Inhibitors.Current topics in medicinal chemistry · 2016Review
- Manipulating miRNA Expression: A Novel Approach for Colon Cancer Prevention and Chemotherapy.Current pharmacology reports · 2015Article
- Epigenetic regulation of inflammatory gene expression in macrophages by selenium.The Journal of nutritional biochemistry · 2015Article
- Kynurenine aminotransferase III and glutamine transaminase L are identical enzymes that have cysteine S-conjugate β-lyase activity and can transaminate L-selenomethionine.The Journal of biological chemistry · 2014Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Methylselenocysteine (MSC) and selenomethionine (SM) are two organoselenium compounds receiving interest for their potential anticancer properties. These compounds can be converted to beta-methylselenopyruvate (MSP) and alpha-keto-gamma-methylselenobutyrate (KMSB), alpha-keto acid metabolites that share structural features with the histone deacetylase (HDAC) inhibitor butyrate. We tested the organoselenium compounds in an in vitro assay with human HDAC1 and HDAC8; whereas SM and MSC had little or no activity up to 2 mM, MSP and KMSB caused dose-dependent inhibition of HDAC activity. Subsequent experiments identified MSP as a competitive inhibitor of HDAC8, and computational modeling supported a mechanism involving reversible interaction with the active site zinc atom. In human colon cancer cells, acetylated histone H3 levels were increased during the period 0.5-48 h after treatment with MSP and KMSB, and there was dose-dependent inhibition of HDAC activity. The proportion of cells occupying G(2)/M of the cell cycle was increased at 10-50 microM MSP and KMSB, and apoptosis was induced, as evidenced by morphological changes, Annexin V staining and increased cleaved caspase-3, -6, -7, -9 and poly(adenosine diphosphate-ribose)polymerase. P21WAF1, a well-established target gene of clinically used HDAC inhibitors, was increased in MSP- and KMSB-treated colon cancer cells at both the messenger RNA and protein level, and there was enhanced P21WAF1 promoter activity. These studies confirm that in addition to targeting redox-sensitive signaling molecules, alpha-keto acid metabolites of organoselenium compounds alter HDAC activity and histone acetylation status in colon cancer cells, as recently observed in human prostate cancer cells.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.