Introduction

Selenium as an Antioxidant
 

Selenium as a Cancer Preventive Agent

Sources of selenium

Brassica Vegetables

Selenium as a cancer preventive agent

Therapeutic nature of selenium

Animals fed diets elevated in selenium have repressed carcinogenesis in many different tumor models (El-Bayoumy 1991; Ip and Hayes 1989). Many of these animal studies were carried out using the inorganic form of selenium, sodium selenite. Yet we know that the majority of selenium contained in foodstuffs and ingested by humans is in organic forms.

The relationship between the form of selenium and its contribution to chemoprevention has been exquisitely demonstrated by Ip and Ganther (1992a; 1992b). Not only is the particular chemical form of selenium important but also the point where the compound enters the selenium metabolic processing pathway (Ip and Ganther 1992a). The most biologically active selenium compound was found to be methylselenocysteine (MSC) followed by selenite and then selenomethione (Ip and Ganter 1992a; 1992b; Ip et al. 1991; Ip and Hayes 1989; Thompson et al. 1994). Both selemomethionine and selenite are marketed as nutritional supplements today for their chemopreventive traits, even though there is uncertainity over a dosage which achieves chemoprevention without toxicity (Ip and Lisk 1994b). Selenite, which has a plus four valance state, promotes free-radical formation due to its oxidative nature and is mutagenic (Whiting 1981; Yan and Spallholz 1993). Whereas the selenium amino acids, selenomethionine and MSC, are stable, non-oxidizing, and nonmutagenic.

Selenium compounds such as MSC which enter the selenium metabolic pathway after the point of being incorporated into selenoproteins as selenocysteine, have a higher likelihood of generating mono and di methylated selenium compounds, such as methylselenol and dimethylselenol, which in turn have greater anticarcinogenic activity (Ip et al. 1991). Furthermore, MSC occurs naturally in plants (Shrift 1973) and has low cellular toxicity (Ip and Ganther 1992a; 1992b; Ip et al. 1991).

Mechanism of action

It is known that selenium inhibits the growth of mammalian cells but how this occurs is not known. There have been many mechanisms proposed, including inhibition of nucleic acid synthesis (Abdullaev et al. 1992), inhibition of transcription factor AP-1 DNA binding (Spyrou et al. 1995), induction of p53 (Lanfear et al. 1994), apoptosis (Lu et al. 1994), and DNA strand breaks (Wilson et al. 1992). Several detailed studies have reported suggestive evidence that the mechanism by which MSC inhibits cancer cell growth is distinct from that of selenite (Sinha et al. 1997; Sinha et al. 1996; Lu et al. 1995). It appears that MSC arrests mammary cells in the S phase of the cell cycle by suppressing the level of cdk2 kinase activity which ultimately results in apoptosis (Sinha et. al. 1997). Another group using a mammary tumor cell line, showed that MSC arrested cell growth in the G1 phase of the cell cycle (Lu et al. 1996). How this selenium-induced cell cycle arrest relates to a functioning human body is unknown.