Document Detail


Green tea polyphenols increase p53 transcriptional activity and acetylation by suppressing class I histone deacetylases.
MedLine Citation:
PMID:  22552582     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Acetylation of the tumor suppressor gene p53 at the carboxy-terminal lysine (Lys) residues enhances its transcriptional activity associated with cell cycle arrest and apoptosis. Histone deacetylases (HDACs), a family of evolutionarily conserved enzymes, counterbalance the acetylation of lysine residues on histone and non-histone proteins. In this study, we demonstrate that green tea polyphenols (GTPs) and their major constituent, (-) epigallocatechin-3-gallate (EGCG), activate p53 through acetylation at the Lys373 and Lys382 residues by inhibiting class I HDACs in LNCaP human prostate cancer cells. Treatment of cells with GTPs (2.5-10 µg/ml) and EGCG (5-20 µM) resulted in dose- and time-dependent inhibition of class I HDACs (HDAC1, 2, 3 and 8), albeit at varying levels. Discontinuation of treatment with GTP/EGCG resulted in the loss of p53 acetylation at both the sites in these cells. GTP/EGCG treatment also resulted in increased expression of p21/waf1 and Bax at the protein and message levels in these cells. The increased GTP/EGCG-mediated p53 acetylation enhanced its binding on the promoters of p21/waf1 and Bax, which was associated with increased accumulation of cells in the G0/G1 phase of the cell cycle and induction of apoptosis. Our findings indicate that GTP/EGCG causes acetylation of p53 by inhibiting class I HDACs, a function that is likely to be part of the mechanisms that control the physiological activity of p53.
Authors:
Vijay S Thakur; Karishma Gupta; Sanjay Gupta
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-04-26
Journal Detail:
Title:  International journal of oncology     Volume:  41     ISSN:  1791-2423     ISO Abbreviation:  Int. J. Oncol.     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-05-09     Completed Date:  2012-08-31     Revised Date:  2013-06-25    
Medline Journal Info:
Nlm Unique ID:  9306042     Medline TA:  Int J Oncol     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  353-61     Citation Subset:  IM    
Affiliation:
Department of Urology and Nutrition, Case Western Reserve University, Cleveland, OH 44106, USA.
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MeSH Terms
Descriptor/Qualifier:
Acetylation
Apoptosis
Camellia sinensis / chemistry*
Catechin / analogs & derivatives*,  pharmacology
Cell Line, Tumor
Cyclin-Dependent Kinase Inhibitor p21 / genetics,  metabolism
G1 Phase Cell Cycle Checkpoints / drug effects
Gene Expression / drug effects
Histone Deacetylase Inhibitors / pharmacology*
Histone Deacetylases / genetics,  metabolism
Humans
Male
Plant Extracts / pharmacology*
Polyphenols / pharmacology*
Promoter Regions, Genetic
Prostatic Neoplasms
Protein Binding
Protein Processing, Post-Translational
Protein Stability
Transcriptional Activation / drug effects*
Tumor Suppressor Protein p53 / genetics,  metabolism,  physiology
bcl-2-Associated X Protein / genetics,  metabolism
Grant Support
ID/Acronym/Agency:
R01 CA115491/CA/NCI NIH HHS; R01 CA115491/CA/NCI NIH HHS; R21 CA109424/CA/NCI NIH HHS; R21 CA109424/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/BAX protein, human; 0/CDKN1A protein, human; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Histone Deacetylase Inhibitors; 0/Plant Extracts; 0/Polyphenols; 0/TP53 protein, human; 0/Tumor Suppressor Protein p53; 0/bcl-2-Associated X Protein; 154-23-4/Catechin; BQM438CTEL/epigallocatechin gallate; EC 3.5.1.98/Histone Deacetylases
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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