Sodium selenite inhibits interleukin-6-mediated androgen receptor activation in prostate cancer cells via upregulation of c-Jun.
BACKGROUND
It has been suggested that interleukin-6 (IL-6) may modulate androgen receptor (AR) action to accelerate prostate cancer (PCa) progression. Selenium compounds are highly recommended as a promising chemopreventive agent for PCa. This study was to determine if selenium can repress IL-6 mediated AR action in PCa progression.


METHODS
Cell proliferation, prostate-specific antigen, gene transfer, and Western blot assays were used to study the effects of sodium selenite and methylseleninic acid on IL-6 mediated AR action on an AR expressing human prostate cancer cell line, LNCaP.


RESULTS
We found that sodium selenite, but not methylseleninic acid, significantly (p<0.05) inhibited IL-6-induced trans-activating activity of AR and cell proliferation in LNCaP cells. Interestingly, although sodium selenite did not show effect on activation of both STAT3 and ERK1/2 in the presence of IL-6, an increased expression of c-Jun was detected in cells after treatment with sodium selenite. Indeed, we showed overexpression of c-Jun blocked IL-6-induced AR activation.


CONCLUSIONS
Taken together, our results suggest that sodium selenite not methylseleninic acid can inhibit IL-6-mediated AR activation by increased c-Jun in LNCaP cells. Sodium selenite may be a proper selenium form for further testing its potency on intervening IL-6-mediated PCa progression.
Gazi
Mozammel H
MH
Department of Urology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
Gong
Aiyu
A
Donkena
Krishna V
KV
Young
Charles Y F
CY
D000728:Androgens / Q000494:pharmacology; D015153:Blotting, Western; D049109:Cell Proliferation; D017930:Genes, Reporter; D006801:Humans; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D019947:Receptors, Interleukin-6 / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D018038:Sodium Selenite / Q000494:pharmacology*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D000093242:Interleukin-6 Inhibitors
D000728:Androgens; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D017430:Prostate-Specific Antigen; D016755:Proto-Oncogene Proteins c-jun; D011944:Receptors, Androgen; D019947:Receptors, Interleukin-6; D050796:STAT3 Transcription Factor; D018038:Sodium Selenite; D000093242:Interleukin-6 Inhibitors; C410798:AR protein, human