Selenium Metabolism in Cancer Cells: The Combined Application of XAS and XFM Techniques to the Problem of Selenium Speciation in Biological Systems

Abstract

Determining the speciation of selenium in vivo is crucial to understanding the biological activity of this essential element, which is a popular dietary supplement due to its anti-cancer properties. Hyphenated techniques that combine separation and detection methods are traditionally and effectively used in selenium speciation analysis, but require extensive sample preparation that may affect speciation. Synchrotron-based X-ray absorption and fluorescence techniques offer an alternative approach to selenium speciation analysis that requires minimal sample preparation. We present a brief summary of some key HPLC-ICP-MS and ESI-MS/MS studies of the speciation of selenium in cells and rat tissues. We review the results of a top-down approach to selenium speciation in human lung cancer cells that aims to link the speciation and distribution of selenium to its biological activity using a combination of X-ray absorption spectroscopy (XAS) and X-ray fluorescence microscopy (XFM). The results of this approach highlight the distinct fates of selenomethionine, methylselenocysteine and selenite in terms of their speciation and distribution within cells: organic selenium metabolites were widely distributed throughout the cells, whereas inorganic selenium metabolites were compartmentalized and associated with copper. New data from the XFM mapping of electrophoretically-separated cell lysates show the distribution of selenium in the proteins of selenomethionine-treated cells. Future applications of this top-down approach are discussed.

Selenium for preventing cancer

“…selenomethionine, selenocysteine) and inorganic forms (e.g. selenate, selenite) (Gammelgaard 2011; Weekley 2013). Selenium yeast refers to a selenium-enriched yeast medium that usually contains nearly entirely organically bound selenium with a high proportion of selenomethionine (Block 2004; Rayman 2004).…”

“…For example, the US Institute of Medicine recommends a daily intake of 55 μg/d for adults (Institute of Medicine 2009), whereas the WHO recommends values ranging from 25 to 34 μg/d, depending on age and sex (WHO 2004). These various standards do not take into account the chemical forms of selenium, despite growing evidence of the importance of selenium speciation (Vinceti 2013a; Vinceti 2013c; Weekley 2013). …”

“…However, such effects are still inadequately investigated (Vinceti 2001; Vinceti 2009). Furthermore, strong evidence shows different biological activities of the various organic and inorganic forms of selenium (Hazane-Puch 2013; Rayman 2008a; Vinceti 2009; Vinceti 2013c; Weekley 2013), suggesting the opportunity to better char-acterise the specific toxicological and nutritional properties of each selenium species in humans, in animals and in the environment. Recent publications have questioned the adequacy of the current upper ’safe’ limit of intake (Jerome-Morais 2011; Morris 2013; Moyad 2012; Rocourt 2013; Sacco 2013; Vinceti 2009; Vinceti 2013b) and have espoused the need to set different limits for the many different sources of organic and inorganic selenium.…”

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

“…For instance, it is admitted that the effects of selenium are strongly dependent upon its chemical form (54). Metabolization of seleno-compounds in vivo gives rise to multiple different metabolites.…”

XAS studies of Se speciation in selenite-fed rats

“…10 Understanding the metabolism and speciation of different Se compounds in vivo is necessary for better understanding their varying biological activities. 11 The gap between the efficacies of Se supplementation observed in laboratory studies and in clinical trials may be due, at least in part, to the choice of Se species used in clinical trials. Selenomethionine (SeMet) or selenised yeast (often containing SeMet and other organic Se compounds) are common choices, 12 yet selenite and methylated Se species such as methylselenocysteine (MeSeCys) and methylseleninic acid (MeSeA) are effective chemopreventative compounds in animal studies 5,6,13 – more effective than SeMet.…”