High Selenium Reduces NF-κB-Regulated Gene Expression in Uninduced Human Prostate Cancer Cells

Abstract

Nuclear factor kappa B (NF-κB) 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-κ B activation in early prostate cancer cells in the absence of exogenously added inducers of the NF-κB 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 μM. Compared to 50 nM Se, treatment with 7.6 μM Se virtually eliminated NF-κB binding to its DNA response element and reduced transcription rates and mRNA levels by half for NF-κB-regulated genes. There were no differences due to Se in tyrosine phosphorylation, inhibitor of kappa B alpha (IκBα) levels, or NF-κB translocation from cytosol to nucleus. The observation in these basal, unstimulated cells of altered NF-κB binding to DNA in the absence of effects on the NF-κB activation pathway suggests an interaction of Se with the NF-κB protein or an effect on recruitment of NF-κB 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.