Suppression of the androgen receptor function by quercetin through protein-protein interactions of Sp1, c-Jun, and the androgen receptor in human prostate cancer cells

Mol Cell Biochem. 2010 Jun;339(1-2):253-62. doi: 10.1007/s11010-010-0388-7. Epub 2010 Feb 11.

Abstract

We have previously reported that the increase in c-Jun expression induced by quercetin inhibited androgen receptor (AR) transactivation, and Sp1 was involved in quercetin-mediated downregulation of AR activity. Transient transfection assays in this work revealed that co-expression of c-Jun quenched Sp1-induced production of luciferase activity driven by AR promoter or three copies of Sp1 binding elements in the AR promoter. Moreover, c-Jun repressed AR-mediated luciferase activity via androgen-response elements (AREs) of the hK2 gene, while this suppression could be restored partially by cotransfection of Sp1 expression plasmid. The physical associations of c-Jun, Sp1, and AR induced by quercetin were further demonstrated by co-immunoprecipitation experiments. In addition, quercetin-mediated repression of AR expression and activity was partially reversed by blocking of JNK signaling pathway. These results suggested that c-Jun might play an important role in the suppression of AR expression and activity in the presence of quercetin, and association of a c-Jun/Sp1/AR protein complex induced by quercetin represented a novel mechanism that was involved in down-regulation of the AR function in prostate cancer cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androgen Receptor Antagonists
  • Antioxidants / pharmacology*
  • Blotting, Western
  • Humans
  • Immunoprecipitation
  • Male
  • Promoter Regions, Genetic / genetics
  • Prostate-Specific Antigen / metabolism
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / metabolism*
  • Proto-Oncogene Proteins c-jun / metabolism*
  • Quercetin / pharmacology*
  • Receptors, Androgen / genetics
  • Receptors, Androgen / metabolism*
  • Sp1 Transcription Factor / metabolism*
  • Transcription, Genetic
  • Transcriptional Activation
  • Tumor Cells, Cultured

Substances

  • AR protein, human
  • Androgen Receptor Antagonists
  • Antioxidants
  • Proto-Oncogene Proteins c-jun
  • Receptors, Androgen
  • Sp1 Transcription Factor
  • Quercetin
  • Prostate-Specific Antigen