Selenium compounds show much promise in the prevention of prostate and other human
cancers. Various
selenium chemical forms have been shown to differ widely in their anticancer properties. The main dietary form is
selenomethionine, which we showed modulated p53 activity by causing redox regulation of key p53
cysteine residues. In the current study we included other
selenium chemical forms,
sodium selenite and methyl-
seleninic acid. All three forms are relevant
selenium sources in human populations. All three forms can affect p53 activity defined as trans-activation of a p53-dependent reporter gene. In addition to the reduction of
cysteine sulfhydryl groups, p53 phosphorylation was also affected in cells treated with
selenium compounds. Methyl-
seleninic acid caused phosphorylation of one or more p53
threonine residues, but did not affect any known
serine phosphorylation sites. By contrast
sodium selenite caused phosphorylation of p53 serines 20, 37 and 46 known to mediate apoptosis.
Selenomethionine did not cause detectable phosphorylation of p53 serines or threonines. Our data show that, although p53 modulation may be a common denominator of
selenium compounds, specific mechanisms of p53 activation differ among
selenium chemical forms. Post-translational modifications of p53 are determinants of p53 activity and probably affect the threshold for p53-mediated functions. Different
selenium chemical forms may differentially modify p53 for DNA repair or apoptosis in conjunction with a given level of endogenous or exogenous DNA damage.