Effect of anti-histone acetyltransferase activity from Rosa rugosa Thunb. (Rosaceae) extracts on androgen receptor-mediated transcriptional regulation.
BACKGROUND
Rosa rugosa Thunb. (Rosaceae) has been traditionally used for treatments of diabetes, chronic inflammatory diseases, pain, and anticancer in Korea.


OBJECTIVE
We investigate the inhibitory effect of histone acetyltransferase activity from the methanol extract of stems of Rosa rugosa on androgen receptor-mediated transcriptional regulation.


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.


CONCLUSIONS
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.
Lee
Yoo-Hyun
YH
Department of Food Science and Nutrition, The University of Suwon, Kyunggi-do, South Korea.
Jung
Myung Gu
MG
Kang
Hee Bum
HB
Choi
Kyung-Chul
KC
Haam
Seungjoo
S
Jun
Woojin
W
Kim
Young-Jun
YJ
Cho
Hong Yon
HY
Yoon
Ho-Geun
HG
D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D051548:Histone Acetyltransferases / Q000037:antagonists & inhibitors*; D006801:Humans; D008297:Male; D010936:Plant Extracts / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000473:pathology; D011944:Receptors, Androgen / Q000502:physiology*; D027826:Rosa / Q000737:chemistry; D014158:Transcription, Genetic
C410798:AR protein, human; D004791:Enzyme Inhibitors; D010936:Plant Extracts; D011944:Receptors, Androgen; D051548:Histone Acetyltransferases