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- W2476446090 abstract "Green tea polyphenols (GTPs) and its major constituent (-)-epigallocatechin-3-gallate (EGCG) reactivate epigenetically silenced genes in cancer cells. Glutathione S-transferase P1 (GSTP1), an enzyme involved in detoxification process, is frequently inactivated in prostate cancer due to epigenetic modifications. The mechanisms underlying the re-expression of GSTP1 expression by GTP/EGCG in prostate cancer is currently not well understood. Earlier we demonstrated the ability of GTP/EGCG to increase p53 transcriptional activity through suppression of class I histone deacetylases (Carcinogenesis 33(2):377-84, 2012). Here we report that the GSTP1 gene is an unrecognized downstream transcriptional target of the tumor suppressor p53, and that GTP/EGCG has ability to increase GSTP1 expression mediated through p53. Treatment of human prostate cancer LNCaP cells with 5μg/ml GTP and 20μM EGCG, activate p53 through acetylation at the Lys373 and Lys382 residues along with consequent increase in GSTP1 protein expression in time-dependent manner. To study the possible interaction between GSTP1 and p53, LNCaP cells stably-transfected with short hairpin-RNA against p53 (LNCaPshp53) and control vector (LNCaPshV) for generation of p53 knockout cells. GTP/EGCG treatment induced p53 activation and acetylation at p53 Lys373 and Lys382 specifically in LNCaPshV cells in time-dependent manner, but not in LNCaPshp53. This increase in p53 acetylation led to activation of GSTP1 in LNCaPshV cells both at protein and message levels. GTP/EGCG-mediated increase in GSTP1 expression is caused by increase binding of p53 to its consensus binding site on the intron 4 of GSTP1 gene as analyzed by electrophoretic mobility shift binding assay. Furthermore, this association was validated by ChIP assay where GTP/EGCG treatment led to an increase in the amount of acetylated p53-Lys373 associated within the intron site of GSTP1, compared to untreated controls. Taken together, our findings indicate the ability of p53 to transcriptionally activate the human GSTP1 gene, which defines a novel mechanism of protection of the genome by green tea polyphenols. Citation Format: Vijay S. Thakur, Gauri Deb, Mark W. Jackson, Sanjay Gupta. Upregulation of glutathione S-transferase P1 by green tea polyphenols: A novel transcriptional target of p53 tumor suppressor gene. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5257." @default.
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- W2476446090 date "2016-07-15" @default.
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- W2476446090 title "Abstract 5257: Upregulation of glutathione S-transferase P1 by green tea polyphenols: A novel transcriptional target of p53 tumor suppressor gene" @default.
- W2476446090 doi "https://doi.org/10.1158/1538-7445.am2016-5257" @default.
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