The Effect of Organoselenium Compounds on Histone Deacetylase Inhibition and Their Potential for Cancer Therapy

Abstract

Genetic and epigenetic changes alter gene expression, contributing to cancer. Epigenetic changes in cancer arise from alterations in DNA and histone modifications that lead to tumour suppressor gene silencing and the activation of oncogenes. The acetylation status of histones and non-histone proteins are determined by the histone deacetylases and histone acetyltransferases that control gene transcription. Organoselenium compounds have become promising contenders in cancer therapeutics. Apart from their anti-oxidative effects, several natural and synthetic organoselenium compounds and metabolites act as histone deacetylase inhibitors, which influence the acetylation status of histones and non-histone proteins, altering gene transcription. This review aims to summarise the effect of natural and synthetic organoselenium compounds on histone and non-histone protein acetylation/deacetylation in cancer therapy.

Seleno-Metabolites and Their Precursors: A New Dawn for Several Illnesses?

“…The significant role of methylselenol in antitumoral treatment lies in its capacity to induce cell death and it is recognized as one of the most cytotoxic Se compounds [23, 72,188,190,191]. Likewise, MSP also exhibits interesting properties, such as its ability to inhibit angiogenesis and histone deacetylase (HDAC) [72,192,193]. The cytotoxic activity of MSC has been determined in a wide range of in vitro studies in different human cancer cell lines, such as breast, esophagus, liver, lung, ovarian, and head and neck squamous cells [63,72,158,190,192,194,195].…”

“…Likewise, MSP also exhibits interesting properties, such as its ability to inhibit angiogenesis and histone deacetylase (HDAC) [72,192,193]. The cytotoxic activity of MSC has been determined in a wide range of in vitro studies in different human cancer cell lines, such as breast, esophagus, liver, lung, ovarian, and head and neck squamous cells [63,72,158,190,192,194,195]. Furthermore, it has been shown to deplete the levels of the vascular endothelial growth factor (VEGF) and the hypoxia-inducible factor-1-α (HIF1-α) in various cell cultures and animal models [63,193,196,197].…”

Preparative Biocatalytic Synthesis of α-Ketomethylselenobutyrate—A Putative Agent for Cancer Therapy

“…Inorganic and organic derivatives of selenium and derivatives of the amino acids Semethylselenocysteine and selenomethionine are also considered to be probable antitumor agents [14,29]. However, if inorganic selenium compounds are toxic and can cause a genotoxic effect, systemic toxicity, or the risk of metastatic formations, then its organic derivatives retain high antitumor activity and the ability to prevent cancer metastasis, and have fewer side effects and less pronounced systemic effects [30,31].…”

“…Another important approach to the treatment of cancer is the search and development of targeted selenium-containing inhibitors. This relatively new class of anticancer drugs includes histone deacetylase (HDAC) inhibitors, which are able to induce apoptosis and induce cell cycle arrest in cancer cells [29]. This group of substances includes α-ketomethylselenobutyrate (KMSB), which structurally resembles short-chain fatty acids (for example, butyric acid) and is an HDAC inhibitor [33].…”

Unexpected kinetically controlled organoselenium-based isomaleimide: X-ray structure, hirshfeld surface analysis, 3D energy framework approach, and density functional theory calculation

“…Recently, OSe compounds have become promising candidates in cancer therapeutics (He et al, 2020). They have also manifested good histone deacetylase inhibitor activity (Adimulam et al, 2021). On the other hand, OSe compounds were extensively used as semiconductors in advanced materials, including photovoltaic cells and sodium-ion batteries and catalysts for the H 2 evolution (Arora et al, 2021).…”