TY - JOUR
T1 - Histone Acetyltransferase Inhibitory Activity of Bokbunja (Rubus coreanus Miq.) ethanol extract on androgen receptor-dependent prostate cancer cell growth
AU - Kim, Mi Jeong
AU - Seong, Ah Reum
AU - Lee, Yoo Hyun
AU - Kim, Young Jun
AU - Shiota, Masaki
AU - Yokomizo, Akira
AU - Naito, Seiji
AU - Lee, Jeongmin
AU - Jun, Woojin
AU - Yoon, Ho Geun
N1 - Funding Information:
Acknowledgments This work was supported by a grant (Code #20070301034007) from BioGreen 21 Program, Rural Development Administration, Republic of Korea; by National Foundation grant funded by the Korea government (MEST) (No. 2010-0028367).
PY - 2010
Y1 - 2010
N2 - In this study, we demonstrate that a bokbunja (Rubus coreanus) ethanol extract (RCE) exhibits the strong histone acetyltransferase (HAT) inhibitory activity, and shows specificity against the p300 HAT enzyme. RCE specifically inhibited p300 acetyltransferase activities with an IC50 of approximately 70 μg/mL, but did not inhibit other epigenetic enzymes. We found that RCE inhibited agonist-dependent androgen receptor (AR) acetylation and suppressed androgen-induced AR transcriptional activity. RCE treatment also decreased the enhancement of AR transcriptional activity caused by p300 overexpression, and combined treatment with RCE potentiated the activity of the AR antagonist flutamide. Finally, RCE treatment reduced the growth of LNCaP human prostate cancer cells via inhibition of cyclin D1 and cyclin E expression, and concomitantly induced apoptosis. Collectively, our results suggest that therapeutic targeting of AR acetylation by HATi could lead to a new class of antagonists for the treatment of prostate cancer.
AB - In this study, we demonstrate that a bokbunja (Rubus coreanus) ethanol extract (RCE) exhibits the strong histone acetyltransferase (HAT) inhibitory activity, and shows specificity against the p300 HAT enzyme. RCE specifically inhibited p300 acetyltransferase activities with an IC50 of approximately 70 μg/mL, but did not inhibit other epigenetic enzymes. We found that RCE inhibited agonist-dependent androgen receptor (AR) acetylation and suppressed androgen-induced AR transcriptional activity. RCE treatment also decreased the enhancement of AR transcriptional activity caused by p300 overexpression, and combined treatment with RCE potentiated the activity of the AR antagonist flutamide. Finally, RCE treatment reduced the growth of LNCaP human prostate cancer cells via inhibition of cyclin D1 and cyclin E expression, and concomitantly induced apoptosis. Collectively, our results suggest that therapeutic targeting of AR acetylation by HATi could lead to a new class of antagonists for the treatment of prostate cancer.
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U2 - 10.1007/s10068-010-0214-8
DO - 10.1007/s10068-010-0214-8
M3 - Article
AN - SCOPUS:79959703181
SN - 1226-7708
VL - 19
SP - 1503
EP - 1511
JO - Food Science and Biotechnology
JF - Food Science and Biotechnology
IS - 6
ER -
