GSTT2, a phase II gene induced by apple polyphenols, protects colon epithelial cells against genotoxic damage

Abstract

The potential protective effect of a polyphenol-rich diet for colon carcinogenesis is of great scientific and medical interest. Apples are a main source of polyphenols, and apple juice has been shown to attenuate chemically induced colon carcinogenesis in animal models. In addition to an antioxidant and antiproliferative activity, apple polyphenols have been shown to elevate expression of the phase II gene glutathione S-transferase T2 (GSTT2) in colon epithelial cells. We hypothesized that apple polyphenols may thereby provide protection against oxidant-induced DNA damage. Using GSTT2 promoter constructs and luciferase reporter assays, we found that polyphenolic apple extracts (AE) can directly enhance GSTT2 promoter activity. Comet assays demonstrated that the genotoxicity of the GSTT2 substrate cumene hydroperoxide (CumOOH) was significantly reduced when HT29 colon epithelial cells were pretreated with AE. Overexpression of GSTT2 in HT29 cells significantly reduced CumOOH induced DNA damage, whereas shRNA mediated knockdown of GSTT2 gene expression resulted in higher damage. Our results causally link GSTT2 levels with protection from genotoxic stress, and provide evidence that the antigenotoxic effects of apple polyphenols in vitro are at least in part due to an induction of GSTT2 expression. Induction of phase II genes may contribute to primary chemoprevention of colon cancer by apple polyphenols.

Histone Methyltransferase Setd7 Regulates Nrf2 Signaling Pathway by Phenethyl Isothiocyanate and Ursolic Acid in Human Prostate Cancer Cells

“…Petermann et al reported that Gstt2 protects cells from oxidative DNA damage induced by the synthetic hydroperoxide CumOOH, indicating that Gstt2 has anti-genotoxic function. [45] Therefore, we addressed the question of whether Setd7 protects against genotoxic stress by stabilizing Gstt2 expression. To analyze this, we challenged LNCaP and PC-3 cells with the Gstt2 substrate CumOOH.…”

Predictive model for the reduction of heat resistance of Listeria monocytogenes in ground beef by the combined effect of sodium chloride and apple polyphenols

“…Apple polyphenols (a) inactivated pathogenic organisms in laboratory media (Fattouch et al, 2008;Wong et al, 2008;Du et al, 2011;Fratianni et al, 2011Fratianni et al, , 2012Friedman et al, 2013); (b) inactivated pathogenic bacteria on leafy greens (Moore et al, 2011) and in grilled beef patties (Rounds et al, 2012); (c) inhibited the biological activities of bacterial Shiga 2 toxin (Quiñones et al, 2009;Rasooly et al, 2010); (d) protected mice against infection by the influenza virus (He et al, 2011); and (e) protected cells against carcinogenic and genotoxic damage (Gerhauser, 2008;Petermann et al, 2009). …”

Impact of apple polyphenols on GSTT2 gene expression, subsequent protection of DNA and modulation of proliferation using LT97 human colon adenoma cells

“…Neither AE[B] nor SPM induced GSTT2 or protected against CumOOH-induced DNA damage. Thus, we could not confirm a causal correlation between GSTT2 upregulation and protection against CumOOH found by others in genetically modified cells [52].…”