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.
Christensen
Merrill J
MJ
Department of Nutrition, Dietetics, and Food Science, Brigham Young University, Provo, UT 84602, USA. merrill_christensen@byu.edu
Nartey
Edward T
ET
Hada
Aimee L
AL
Legg
Russell L
RL
Barzee
Brett R
BR
D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000517:prevention & control; D012333:RNA, Messenger / Q000378:metabolism; D012643:Selenium / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000975:Antioxidants; D004268:DNA-Binding Proteins; D016328:NF-kappa B; D012333:RNA, Messenger; D012643:Selenium