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.
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.
Department of Biochemistry and Molecular Biology, School of Medicine, Shandong University, 44 Wenhua westroad, 250012 Jinan, China. lyuanhq@sdu.edu.cn
Huiqing
H
Yuan
Charles Y F
CY
Young
Yuanyuan
Y
Tian
Zhifang
Z
Liu
Mengye
M
Zhang
Hongxiang
H
Lou
D059002:Androgen Receptor Antagonists; D000975:Antioxidants / Q000494:pharmacology*; D015153:Blotting, Western; D006801:Humans; D047468:Immunoprecipitation; D008297:Male; D011401:Promoter Regions, Genetic / Q000235:genetics; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D011794:Quercetin / Q000494:pharmacology*; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
C410798:AR protein, human; D059002:Androgen Receptor Antagonists; D000975:Antioxidants; D016755:Proto-Oncogene Proteins c-jun; D011944:Receptors, Androgen; D016329:Sp1 Transcription Factor; D011794:Quercetin; D017430:Prostate-Specific Antigen