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 $IC_{50}$ of approximately 70 ${mu}g$/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.