Anti-histone acetyltransferase activity from allspice extracts inhibits androgen receptor-dependent prostate cancer cell growth.
Histone acetylation depends on the activity of two enzyme families, histone acetyltransferase (HAT) and deacetylase (HDAC). In this study, we screened various plant extracts to find potent HAT inhibitors. Hot water extracts of allspice inhibited HAT activity, especially p300 and CBP (40% at 100 microg/ml). The mRNA levels of two androgen receptor (AR) regulated genes, PSA and TSC22, decreased with allspice treatment (100 microg/ml). Importantly, in IP western analysis, AR acetylation was dramatically decreased by allspice treatment.Furthermore, chromatin immunoprecipitation indicated that the acetylation of histone H3 in the PSA and B2M promoter regions was also repressed. Finally, allspice treatment reduced the growth of human prostate cancer cells, LNCaP (50% growth inhibition at 200 microg/ml). Taken together, our data indicate that the potent HAT inhibitory activity of allspice reduced AR and histone acetylation and led to decreased transcription of AR target genes, resulting in inhibition of prostate cancer cell growth.
Lee
Yoo-Hyun
YH
Department of Biochemistry and Molecular Biology, Center for Chronic Metabolic Disease Research, College of Medicine, Yonsei University.
Hong
Soon Won
SW
Jun
Woojin
W
Cho
Hong Yon
HY
Kim
Han-Cheon
HC
Jung
Myung Gu
MG
Wong
Jiemin
J
Kim
Ha-Il
HI
Kim
Chang-Hoon
CH
Yoon
Ho-Geun
HG
D000107:Acetylation; D059002:Androgen Receptor Antagonists; D000970:Antineoplastic Agents / Q000494:pharmacology*; D043424:Carboxypeptidase B / Q000037:antagonists & inhibitors / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D051548:Histone Acetyltransferases / Q000037:antagonists & inhibitors*; D006657:Histones / Q000378:metabolism; D006801:Humans; D008297:Male; D027841:Pimenta; D010936:Plant Extracts / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000201:enzymology*; D011944:Receptors, Androgen / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects; D050880:p300-CBP Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics
C410798:AR protein, human; D059002:Androgen Receptor Antagonists; D000970:Antineoplastic Agents; C058173:CPB1 protein, human; D004791:Enzyme Inhibitors; D006657:Histones; D010936:Plant Extracts; D011944:Receptors, Androgen; D051548:Histone Acetyltransferases; D050880:p300-CBP Transcription Factors; D043424:Carboxypeptidase B