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

International Journal of Oncology
Vijay S ThakurSanjay Gupta

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 apo...Continue Reading

References

May 15, 1997·Nature·Y HauptM Oren
Apr 25, 2000·The Journal of Biological Chemistry·L J JuanC W Wu
Nov 8, 2002·The Journal of Biological Chemistry·Muyang LiWei Gu
Nov 12, 2002·The EMBO Journal·Akihiro ItoTso-Pang Yao
Feb 26, 2004·Proceedings of the National Academy of Sciences of the United States of America·Jianyuan LuoWei Gu
Feb 18, 2005·Medicinal Research Reviews·Antonello MaiRino Ragno
Mar 15, 2005·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Kedar HastakMunna L Agarwal
Nov 24, 2006·The Journal of Biological Chemistry·Somdutta Roy, Martin Tenniswood
Dec 7, 2007·British Journal of Pharmacology·F CondorelliP L Canonico
May 20, 2008·Cell·Yi TangWei Gu
Dec 23, 2008·BMC Cancer·Florian R FritzscheGlen Kristiansen
Dec 24, 2008·Cancer Letters·Wilko Weichert
Mar 7, 2009·The Journal of Biological Chemistry·Hirohito YamaguchiHong-Gang Wang
Oct 27, 2009·International Journal of Cancer. Journal International Du Cancer·Mitali PandeySanjay Gupta
Jun 24, 2010·The EMBO Journal·Roel H WiltingJan-Hermen Dannenberg

❮ Previous
Next ❯

Citations

Nov 1, 2012·Cancer Letters·Srinivas Reddy Boreddy, Sanjay K Srivastava
Dec 3, 2014·The Psychiatric Clinics of North America·Simon ChiuRobbie Campbell
Nov 21, 2017·European Journal of Nutrition·Inês FigueiraCláudia N Santos
May 12, 2020·Molecular Carcinogenesis·Eswar ShankarSanjay Gupta
Jan 8, 2021·Journal of Cancer Prevention·Elisabetta DamianiRoderick H Dashwood

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis