Redox-Active Selenium Compounds—From Toxicity and Cell Death to Cancer Treatment

Abstract

Selenium is generally known as an antioxidant due to its presence in selenoproteins as selenocysteine, but it is also toxic. The toxic effects of selenium are, however, strictly concentration and chemical species dependent. One class of selenium compounds is a potent inhibitor of cell growth with remarkable tumor specificity. These redox active compounds are pro-oxidative and highly cytotoxic to tumor cells and are promising candidates to be used in chemotherapy against cancer. Herein we elaborate upon the major forms of dietary selenium compounds, their metabolic pathways, and their antioxidant and pro-oxidant potentials with emphasis on cytotoxic mechanisms. Relative cytotoxicity of inorganic selenite and organic selenocystine compounds to different cancer cells are presented as evidence to our perspective. Furthermore, new novel classes of selenium compounds specifically designed to target tumor cells are presented and the potential of selenium in modern oncology is extensively discussed.

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

“…There exist two key metabolites of Se, which are critical for chemoprevention/ chemotherapy. 48 Hydrogen selenide necessary for the formation of selenoproteins results mainly from inorganic selenocompounds such as selenate or selenite, respectively, and methylselenol, which is generated from organic selenocompounds. In this study, the pro-oxidant MSA, a synthetic selenocompound and precursor of methylselenol, induced MHC class I surface expression not only in B16F10 melanoma cells, but also on several other tumor cell lines, including human cancer cells.…”

Recent advances in the mechanism of selenoamino acids toxicity in eukaryotic cells

“…Today, it is generally admitted that oxidative stress is a determinant factor of selenium cytotoxicity as well as anticarcinogenic properties (17,64). Pro-oxidant properties of selenium originate from the in vivo conversion of seleno-compounds into H 2 Se or into selenols (RSeH: SeCys, MeSe, GSeH,…), which are readily oxidized by oxygen with concomitant generation of ROS (Figure 2A and B) (9,(65)(66)(67)(68).…”

“…Because cancer cells generally exhibit an increased vulnerability to ROS-producing compounds, there is an increasing interest in designing anticancer agents promoting oxidative stress. Among redox active drugs, selenite is a promising candidate as a cancer therapeutic agent (17,151). The next step consists in evaluating its toxicity in cancer patients and the therapeutic potential of redoxactive selenium compounds.…”

“…For the sake of comparison, current knowledge on the mechanism of inorganic selenium toxicity will also be briefly considered, although readers are invited to consult recent reviews on the subject (17)(18)(19)(20).…”

Lithium as a prooxidant? A possible protective role of selenium – in vitro study

“…Inorganic selenium (sodium selenite) has been found to prevent oxidative stress caused by methamphetamine in neuronal cells [5] and by As 2 O 3 in fish hepatoma cells [6], as well as t-butyl hydroperoxide-induced DNA damage in human mesenchymal stromal cells [7]. Other forms (organic compounds and nanoparticles) of selenium have also been studied and the research has revealed the dependence of the effects on the used form [3,[8][9][10].…”