Ethnopharmacological relevance: Rosa rugosa Thunb. (Rosaceae) has been traditionally used for treatments of diabetes, chronic inflammatory diseases, pain, and anticancer in Korea.
Aim of study: We investigate the inhibitory effect of histone acetyltransferase activity from the methanol extract of stems of Rosa rugosa on androgen receptor-mediated transcriptional regulation.
Materials and methods: For the present study, Rosa rugosa methanol extract (RRME) was obtained from stem part of Rosa rugosa using methanol extraction. Histone acetyltransferase assay were performed to measure the inhibitory effect on acetylation, reporter assay, real-time PCR and ChIP assay were performed to measure androgen receptor-mediated transcriptional regulation, and MTT test were performed to measure cell viability.
Results: RRME inhibited both p300 and CBP (60-70% at 100 microg/ml) activity. We show RRME mediates agonist-dependent androgen receptor (AR) activation and suppresses antagonist-dependent inhibition. RRME treatment also decreased transcription of AR regulated genes and also reduced histone H3 and AR acetylation in the promoters of prostate-specific antigen (PSA) and beta-2-microglobulin (B2M). Finally, RRME treatment reduced the growth of LNCaP, a human prostate cancer cell line.
Conclusion: These results demonstrate RRME is a potent HAT inhibitor, which reduced AR and histone acetylation leading to decreased AR-mediated transcription and reduced LNCaP cell growth.