[The roles of c-Jun and CBP in the inhibitory effect of quercetin on prostate cancer cells].
OBJECTIVE
To further uncover the possible mechanism of quercetin-mediated inhibitory effect on prostate cancer cells.


METHODS
The cell extracts treated with quercetin or without treatment were used for checking protein expression levels of c-Jun and cAMP response element binding protein (CREB)-binding protein (CBP) by Western blotting assay. Regulatory effects of c-Jun and CBP on the function of androgen receptor (AR) were examined by cotransfection experiment. Finally, a physical interaction of c-Jun and the AR was investigated by coimmunoprecipitation.


RESULTS
Quercetin dramatically induced the protein expression of c-Jun which in turn inhibited the AR function. Meanwhile, quercetin had no detectable effect on CBP expression, and the results of transient transfection demonstrated that the ectopic CBP stimulated the transcriptional activity of AR, whereas CBP-mediated stimulation could be attenuated by quercetin. Furthermore, physical interaction of c-Jun and the AR was confirmed by coimmunoprecipitation result.


CONCLUSIONS
Overexpression of c-Jun induced by quercetin had inhibitory effect on the function of AR protein, and increased CBP expression did not reverse the inhibition by quercetin. Together, quercetin-mediated inhibition on the AR function might be not by competition with limited amount of CBP in the cell, but through a direct association of c-Jun and the AR.
Yuan
Hui-qing
HQ
Department of Biochemistry and Molecular Biology, School of Medicine, Shandong University, Jinan 250012, China.
Guo
Huai-fang
HF
He
Mei-lan
ML
Kong
Feng
F
Hu
Xiao-Yan
XY
Jiang
An-li
AL
Xu
Xia
X
Zhang
Jian-ye
JY
Charles
Y F Young
YF
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D050882:CREB-Binding Protein / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D045744:Cell Line, Tumor; D006801:Humans; D047468:Immunoprecipitation; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology; D011485:Protein Binding / Q000187:drug effects; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D011794:Quercetin / Q000494:pharmacology*; D011944:Receptors, Androgen / Q000235:genetics / Q000502:physiology; D014162:Transfection
D000972:Antineoplastic Agents, Phytogenic; D016755:Proto-Oncogene Proteins c-jun; D011944:Receptors, Androgen; D011794:Quercetin; D050882:CREB-Binding Protein