High selenium reduces NF-kappaB-regulated gene expression in uninduced human prostate cancer cells.

Nuclear factor kappa B (NF-kappaB) induces expression of antiapoptotic and pro-inflammatory genes and is constitutively activated in prostate cancer. We tested the hypothesis that a biologically and physiologically relevant form and concentration of selenium (Se) may alter NF-kappa B activation in early prostate cancer cells in the absence of exogenously added inducers of the NF-kappaB pathway. LNCaP cells were cultured in medium without added tumor necrosis factor alpha or lipopolysaccharide but with methylseleninic acid added to provide final concentrations of Se of 30 nM-7.6 microM. Compared to 50 nM Se, treatment with 7.6 microM Se virtually eliminated NF-kappaB binding to its DNA response element and reduced transcription rates and mRNA levels by half for NF-kappaB-regulated genes. There were no differences due to Se in tyrosine phosphorylation, inhibitor of kappa B alpha (I kappa B alpha) levels, or NF-kappaB translocation from cytosol to nucleus. The observation in these basal, unstimulated cells of altered NF-kappaB binding to DNA in the absence of effects on the NF-kappaB activation pathway suggests an interaction of Se with the NF-kappaB protein or an effect on recruitment of NF-kappaB coactivators or corepressors. Inhibition of transcription factor binding and anti-apoptotic gene expression may be one mechanism for the chemopreventive effects of Se against prostate cancer.