Premium
Phenethyl isothiocyanate inhibits androgen receptor‐regulated transcriptional activity in prostate cancer cells through suppressing PCAF
Author(s) -
Yu Chunguang,
Gong AiYu,
Chen Dongqing,
Solelo Leon Daniel,
Young Charles YF,
Chen XianMing
Publication year - 2013
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201200810
Subject(s) - phenethyl isothiocyanate , pcaf , androgen receptor , cancer research , carcinogenesis , dihydrotestosterone , cell growth , downregulation and upregulation , chemistry , prostate cancer , biology , transcription factor , microbiology and biotechnology , isothiocyanate , cancer , endocrinology , androgen , biochemistry , genetics , hormone , gene
Scope Androgen receptor ( AR ) signaling is critical for all aspects of prostate growth and tumorigenesis. The glucosinolate‐derived phenethyl isothiocyanate ( PEITC ) has recently been demonstrated to reduce the risk of prostate cancer ( PC a) and inhibit PC a cell growth. We previously reported that p300/ CBP ‐associated factor ( PCAF ), a co‐regulator for AR , is upregulated in PC a cells through suppression of the mir‐17 gene. Here, we assessed the effects of PEITC on PCAF expression and AR ‐regulated transcriptional activity in PC a cells. Methods and results Using AR ‐responsive LNC aP cells, we observed the inhibitory effects of PEITC on the dihydrotestosterone‐stimulated AR transcriptional activity and cell growth of PC a cells. Interestingly, overexpression of PCAF attenuated the inhibitory effects of PEITC on dihydrotestosterone‐stimulated AR transcriptional activity. Expression of PCAF was upregulated in PC a cells through suppression of mi R ‐17. PEITC treatment significantly decreased PCAF expression and promoted transcription of mi R ‐17 in LNC a P cells. Functional inhibition of mi R ‐17 attenuated the suppression of PCAF in cells treated by PEITC . Conclusion Our results indicate that PEITC inhibits AR ‐regulated transcriptional activity and cell growth of PC a cells through mi R ‐17‐mediated suppression of PCAF , suggesting a new mechanism by which PEITC modulates PC a cell growth.