Data obtained on the effects of
selenium compounds on regulatory
transcription factor-
DNA binding by other laboratories are briefly reviewed, and some of our own results in this area are also presented. We assessed the in vitro and in vivo effects of the organoselenium compound
1,4-phenylenebis(methylene)selenocyanate (p-XSC) on the binding activities of the
transcription factors nuclear factor-kappa B (
NF-kappa B),
activator protein-1 (AP-1), Sp1, and Sp3 using the HCT-116 (human colorectal
adenocarcinoma) cell line as a model system. Using nuclear extracts, electrophoretic mobility shift assays were carried out to determine the extent of binding of the
transcription factors to their respective consensus recognition sites on radiolabeled
oligonucleotides. p-XSC and
sodium selenite reduced the consensus site binding activity of
NF-kappa B in a concentration-dependent manner when nuclear extracts from cells stimulated with
tumor necrosis factor-alpha were incubated with either compound ("in vitro"). However, only p-XSC inhibited
NF-kappa B consensus recognition site binding when the cells were pretreated with either compound and were then stimulated with
tumor necrosis factor-alpha ("in vivo"). In contrast, the consensus site binding activity of
AP-1 was inhibited only with
sodium selenite, but not with p-XSC in vitro or in vivo. p-XSC or
sodium selenite reduced the consensus site binding of
transcription factors Sp1 and Sp3 in concentration- and time-dependent manners when nuclear extracts from cells treated with either compound in vivo were assayed by electrophoretic mobility shift assay. 1,4-Phenylenebis(methylene)thiocyanate, the
sulfur analog of p-XSC, which is inactive in
chemoprevention, had no effect on the
oligonucleotide binding of Sp1 and Sp3. Our observations could provide further clues as to the mechanisms involved in the
chemoprevention of
cancer by p-XSC.