Green tea polyphenols increase p53 transcriptional activity and acetylation by suppressing class I histone deacetylases

  • Authors:
    • Vijay S. Thakur
    • Karishma Gupta
    • Sanjay Gupta
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  • Published online on: April 26, 2012     https://doi.org/10.3892/ijo.2012.1449
  • Pages: 353-361
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Abstract

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.

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July 2012
Volume 41 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Thakur VS, Gupta K and Gupta S: Green tea polyphenols increase p53 transcriptional activity and acetylation by suppressing class I histone deacetylases . Int J Oncol 41: 353-361, 2012
APA
Thakur, V.S., Gupta, K., & Gupta, S. (2012). Green tea polyphenols increase p53 transcriptional activity and acetylation by suppressing class I histone deacetylases . International Journal of Oncology, 41, 353-361. https://doi.org/10.3892/ijo.2012.1449
MLA
Thakur, V. S., Gupta, K., Gupta, S."Green tea polyphenols increase p53 transcriptional activity and acetylation by suppressing class I histone deacetylases ". International Journal of Oncology 41.1 (2012): 353-361.
Chicago
Thakur, V. S., Gupta, K., Gupta, S."Green tea polyphenols increase p53 transcriptional activity and acetylation by suppressing class I histone deacetylases ". International Journal of Oncology 41, no. 1 (2012): 353-361. https://doi.org/10.3892/ijo.2012.1449