The roles of c-Jun and CBP in the inhibitory effect of quercetin on prostate cancer cells.
- Author:
Hui-qing YUAN
1
;
Huai-fang GUO
;
Mei-lan HE
;
Feng KONG
;
Xiao-Yan HU
;
An-li JIANG
;
Xia XU
;
Jian-ye ZHANG
;
Y F Young CHARLES
Author Information
- Publication Type:Journal Article
- MeSH: Antineoplastic Agents, Phytogenic; pharmacology; CREB-Binding Protein; genetics; metabolism; physiology; Cell Line, Tumor; Humans; Immunoprecipitation; Male; Prostatic Neoplasms; metabolism; pathology; Protein Binding; drug effects; Proto-Oncogene Proteins c-jun; genetics; metabolism; physiology; Quercetin; pharmacology; Receptors, Androgen; genetics; physiology; Transfection
- From: Acta Pharmaceutica Sinica 2006;41(9):819-824
- CountryChina
- Language:Chinese
-
Abstract:
AIMTo further uncover the possible mechanism of quercetin-mediated inhibitory effect on prostate cancer cells.
METHODSThe 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.
RESULTSQuercetin 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.
CONCLUSIONOverexpression 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.