Sodium selenite inhibits interleukin-6-mediated androgen receptor activation in prostate cancer cells via upregulation of c-Jun

Clin Chim Acta. 2007 May 1;380(1-2):145-50. doi: 10.1016/j.cca.2007.01.031. Epub 2007 Feb 11.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Androgens / pharmacology
  • Blotting, Western
  • Cell Proliferation
  • Genes, Reporter
  • Humans
  • Interleukin-6 / antagonists & inhibitors*
  • Male
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Prostate-Specific Antigen / metabolism
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology
  • Proto-Oncogene Proteins c-jun / metabolism*
  • Receptors, Androgen / genetics
  • Receptors, Androgen / metabolism*
  • Receptors, Interleukin-6 / metabolism*
  • STAT3 Transcription Factor / metabolism
  • Sodium Selenite / pharmacology*
  • Transcription, Genetic
  • Tumor Cells, Cultured
  • Up-Regulation

Substances

  • AR protein, human
  • Androgens
  • Interleukin-6
  • Proto-Oncogene Proteins c-jun
  • Receptors, Androgen
  • Receptors, Interleukin-6
  • STAT3 Transcription Factor
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Prostate-Specific Antigen
  • Sodium Selenite