Anti-histone acetyltransferase activity from allspice extracts inhibits androgen receptor-dependent prostate cancer cell growth

• Published in: Bioscience, biotechnology, and biochemistry Vol. 71; no. 11; pp. 2712 - 2719
• Main Authors: Lee, Y.H.(Yonsei Univ., Seoul (Korea R.)), Hong, S.W, Jun, W, Cho, H.Y, Kim, H.C, Jung, M.G, Wong, J, Kim, H.I, Kim, C.H, Yoon, H.G
• Format: Journal Article
• Language: English
• Published: Tokyo Japan Society for Bioscience, Biotechnology, and Agrochemistry 01.11.2007; Japan Society for Bioscience Biotechnology and Agrochemistry; Oxford University Press
• Subjects: ACETILACION; ACETYLATION; ALLSPICE; androgen receptor; Androgen Receptor Antagonists; ANDROGENE; ANDROGENOS; ANDROGENS; Antineoplastic Agents - pharmacology; ARN MENSAJERO; ARN MESSAGER; Biological and medical sciences; Carboxypeptidase B - antagonists & inhibitors; Carboxypeptidase B - genetics; Cell Line, Tumor; Cell Proliferation - drug effects; CHROMATIN; CHROMATINE; CROMATINA; DISEASES; Drug Screening Assays, Antitumor; ENFERMEDAD; Enzyme Inhibitors - pharmacology; Fundamental and applied biological sciences. Psychology; HISTONAS; HISTONE; histone acetyltransferase; Histone Acetyltransferases - antagonists & inhibitors; HISTONES; Histones - metabolism; Humans; MALADIES; Male; MESSENGER RNA; p300-CBP Transcription Factors - antagonists & inhibitors; p300-CBP Transcription Factors - genetics; PIMENT DE LA JAMAIQUE; Pimenta; PIMIENTA INGLESA; Plant Extracts - pharmacology; prostate cancer; Prostatic Neoplasms - enzymology; Receptors, Androgen - metabolism; Transcriptional Activation - drug effects; Cell proliferation; histone acetyltransferase; Extract; allspice; Malignant tumor; prostate cancer; Androgen receptor; Acetylation; Inhibition; Histone; Prostate; Tumor cell; Cancer; Hormonal receptor
• ISSN: 0916-8451; 1347-6947
• DOI: 10.1271/bbb.70306

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.