Abstract
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 (PCa) and inhibit PCa cell growth. We previously reported that p300/CBP-associated factor (PCAF), a co-regulator for AR, is upregulated in PCa cells through suppression of the mir-17 gene. Here, we assessed the effects of PEITC on PCAF expression and AR-regulated transcriptional activity in PCa cells. Methods and results: Using AR-responsive LNCaP cells, we observed the inhibitory effects of PEITC on the dihydrotestosterone-stimulated AR transcriptional activity and cell growth of PCa cells. Interestingly, overexpression of PCAF attenuated the inhibitory effects of PEITC on dihydrotestosterone-stimulated AR transcriptional activity. Expression of PCAF was upregulated in PCa cells through suppression of miR-17. PEITC treatment significantly decreased PCAF expression and promoted transcription of miR-17 in LNCaP cells. Functional inhibition of miR-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 PCa cells through miR-17-mediated suppression of PCAF, suggesting a new mechanism by which PEITC modulates PCa cell growth.
| Original language | English |
|---|---|
| Pages (from-to) | 1825-1833 |
| Number of pages | 9 |
| Journal | Molecular Nutrition and Food Research |
| Volume | 57 |
| Issue number | 10 |
| DOIs | |
| State | Published - Oct 2013 |
Fingerprint
All Science Journal Classification (ASJC) codes
- Food Science
- Biotechnology
Cite this
Phenethyl isothiocyanate inhibits androgen receptor-regulated transcriptional activity in prostate cancer cells through suppressing PCAF. / Yu, Chunguang; Gong, Ai Yu; Chen, Dongqing; Solelo Leon, Daniel; Young, Charles Yf; Chen, Xian-Ming.
In: Molecular Nutrition and Food Research, Vol. 57, No. 10, 10.2013, p. 1825-1833.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Phenethyl isothiocyanate inhibits androgen receptor-regulated transcriptional activity in prostate cancer cells through suppressing PCAF
AU - Yu, Chunguang
AU - Gong, Ai Yu
AU - Chen, Dongqing
AU - Solelo Leon, Daniel
AU - Young, Charles Yf
AU - Chen, Xian-Ming
PY - 2013/10
Y1 - 2013/10
N2 - 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 (PCa) and inhibit PCa cell growth. We previously reported that p300/CBP-associated factor (PCAF), a co-regulator for AR, is upregulated in PCa cells through suppression of the mir-17 gene. Here, we assessed the effects of PEITC on PCAF expression and AR-regulated transcriptional activity in PCa cells. Methods and results: Using AR-responsive LNCaP cells, we observed the inhibitory effects of PEITC on the dihydrotestosterone-stimulated AR transcriptional activity and cell growth of PCa cells. Interestingly, overexpression of PCAF attenuated the inhibitory effects of PEITC on dihydrotestosterone-stimulated AR transcriptional activity. Expression of PCAF was upregulated in PCa cells through suppression of miR-17. PEITC treatment significantly decreased PCAF expression and promoted transcription of miR-17 in LNCaP cells. Functional inhibition of miR-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 PCa cells through miR-17-mediated suppression of PCAF, suggesting a new mechanism by which PEITC modulates PCa cell growth.
AB - 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 (PCa) and inhibit PCa cell growth. We previously reported that p300/CBP-associated factor (PCAF), a co-regulator for AR, is upregulated in PCa cells through suppression of the mir-17 gene. Here, we assessed the effects of PEITC on PCAF expression and AR-regulated transcriptional activity in PCa cells. Methods and results: Using AR-responsive LNCaP cells, we observed the inhibitory effects of PEITC on the dihydrotestosterone-stimulated AR transcriptional activity and cell growth of PCa cells. Interestingly, overexpression of PCAF attenuated the inhibitory effects of PEITC on dihydrotestosterone-stimulated AR transcriptional activity. Expression of PCAF was upregulated in PCa cells through suppression of miR-17. PEITC treatment significantly decreased PCAF expression and promoted transcription of miR-17 in LNCaP cells. Functional inhibition of miR-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 PCa cells through miR-17-mediated suppression of PCAF, suggesting a new mechanism by which PEITC modulates PCa cell growth.
UR - http://www.scopus.com/inward/record.url?scp=84884918893&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84884918893&partnerID=8YFLogxK
U2 - 10.1002/mnfr.201200810
DO - 10.1002/mnfr.201200810
M3 - Article
C2 - 23661605
AN - SCOPUS:84884918893
VL - 57
SP - 1825
EP - 1833
JO - Molecular Nutrition and Food Research
JF - Molecular Nutrition and Food Research
SN - 1613-4125
IS - 10
ER -