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.
Highlights
The common feature among selenium compounds inhibiting the growth of neoplastic cells is their pronounced and unique redox activity either by the compound itself or by metabolites, where some selenium compounds, as exemplified by Se-methylselenocysteine, are to be considered as prodrugs
There is some consensus within the literature that the monomethylselenide is likely the chemoprevention/anti-cancer selenium metabolite [49] formed from the metabolism of selenomethionine, Se-methylselenocysteine or H2Se, which may redox cycle as hydrogen selenide (HSe), prior to being methylated as methylselenide
It seems obvious that the pro-oxidant functions of many of these redox-active forms of selenium are the key to their anticancer effects
Summary
The common feature among selenium compounds inhibiting the growth of neoplastic cells is their pronounced and unique redox activity either by the compound itself or by metabolites, where some selenium compounds, as exemplified by Se-methylselenocysteine, are to be considered as prodrugs. This redox property is essential for selenium’s antineoplastic effects and the application of selenium compounds in cancer therapeutics. There is a new generation of compounds available and under development that will efficiently deliver redox active cytotoxic selenium to tumor cells These new compounds, together with the well-known natural dietary supplemental compounds, will be discussed in this review. These remarkable effects have been known for more than a century, there are very few clinical trials and until now, to our knowledge, no systematic phase I trial that would make systematic selenium therapeutic evaluation trials possible
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