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Review
. 2015 May 13;7(5):3536-56.
doi: 10.3390/nu7053536.

Redox-active selenium compounds--from toxicity and cell death to cancer treatment

Sougat Misra  1 , Mallory Boylan  2 , Arun Selvam  3 , Julian E Spallholz  4 , Mikael Björnstedt  5
Affiliations
Review

Redox-active selenium compounds--from toxicity and cell death to cancer treatment

Sougat Misra et al. Nutrients. .

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.

Keywords: antioxidants; cancer; cytotoxicity; selenium; selenoproteins; tumor.

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Figures

Figure 1
Figure 1
Effect of elevated level of ROS in normal and cancer cells.
Figure 2
Figure 2
Reaction of selenite with glutathione and subsequent generation of superoxide anion, adapted from [2].
Figure 3
Figure 3
Redox cycling of selenium intermediates in the presence of GSH. Adapted from [27] and later republished [30]. Presented with permission from Taylor and Francis Group.
Figure 4
Figure 4
Quantitative analysis of generation of ROS, superoxide, by selenodiglutathione (left) and by selenite (right) in a lucigenin chemiluminescence-based assay, adapted from [38].
Figure 5
Figure 5
Comparative catalytic oxidation of GSH by isothiocyanates and isoselenocyanates, adapted from [39].
Figure 6
Figure 6
Important selenium methylation reactions and redox species in the maintenance of cell’s redox balance, adapted from [50].
Figure 7
Figure 7
Cytotoxicity of selenite and selenocystine, as measured by a WST-1 assay kit (Roche, Mannheim, Germany), to A549 and H661 cells following 24 h exposure to 22 different selenium concentrations. The highest concentration of selenite and selenocystine was 50 and 200 µM for A549 and H661 cells, respectively. Note that due to low toxicity of selenocystine in H661 cells, the IC50 value should be interpreted carefully.
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