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

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.

Phosphorylation-induced conformational dynamics in an intrinsically disordered protein and potential role in phenotypic heterogeneity

“…Earlier attempts to understand the relationship between AP-1 and AR in PCa had revealed that AP-1 can negatively regulate AR activity (41,42,51), but the role of PAGE4, a remarkably prostate-specific protein expressed only in androgen-dependent cells, had not been suspected, much less considered. The present study has not only uncovered a previously unappreciated role of PAGE4 in driving phenotypic heterogeneity (i.e., responsiveness to androgen in PCa) but also underscores the importance of conformational dynamics of this IDP.…”

Ischemia/reperfusion-induced upregulation of TIGAR in brain is mediated by SP1 and modulated by ROS and hormones involved in glucose metabolism

“…It was reported that SP1 could interact with some steroid receptors (mineralocorticoid receptor, progesterone receptor and androgen receptor) (Meinel et al, 2013;Owen et al, 1998;Yuan et al, 2010), but the accurate interaction between SP1 and these receptors was not clear. SP1 can specifically interact with the TIGAR promoter in liver cancer cells (Zou et al, 2012).…”

Retigeric acid B-induced mitophagy by oxidative stress attenuates cell death against prostate cancer cells in vitro

“…Western blotting assay After treatment as indicated, cell lysates were prepared with RIPA buffer, and the procedures for Western blotting have been described previously [23] . Blots were incubated with the following primary antibodies: LC3B, which was purchased from Novus Biologicals, Inc, USA; Atg5, mTOR, phosphomTOR (Ser2448), Akt, phospho-Akt (Ser473), phospho-p70S6K (Thr389), p62/SQSTM1, DJ-1, and Beclin1, which were from Cell Signal Technology, Inc, USA; Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and poly(ADP-ribose) polymerase (PARP), which were from Santa Cruz Biotechnology, Inc, USA.…”