Phenethyl isothiocyanate inhibits androgen receptor‐regulated transcriptional activity in prostate cancer cells through suppressing PCAF

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.