Title: Epigallocatechin-3-gallate (EGCG) protects against chromate-induced toxicity in vitro.
Authors: Wu, Fen; Sun, Hong; Kluz, Thomas; Clancy, Hailey A; Kiok, Kathrin; Costa, Max
Published In Toxicol Appl Pharmacol, (2012 Jan 15)
Abstract: Hexavalent chromium [Cr(VI)] is a human carcinogen that results in the generation of reactive oxygen species (ROS) and a variety of DNA lesions leading to cell death. Epigallocatechin-3-gallate (EGCG), the major polyphenol present in green tea, possesses potent antioxidative activity capable of protecting normal cells from various stimuli-induced oxidative stress and cell death. Here we demonstrated that co-treatment with EGCG protected human normal bronchial epithelial BEAS-2B cells from Cr(VI)-induced cell death in a dose-dependent manner. Cr(VI) induces apoptosis as the primary mode of cell death. Co-treatment of BEAS-2B cells with EGCG dose-dependently suppressed Cr(VI)-induced apoptosis. Fluorescence microscopic analyses and quantitative measurement revealed that EGCG significantly decreased intracellular levels of ROS induced by Cr(VI) exposure. Using a well-established K(+)/SDS precipitation assay, we further showed that EGCG was able to dose-dependently reduce DNA-protein cross-links (DPC), lesions that could be partially attributed to Cr(VI)-induced oxidative stress. Finally, analyses of Affymetrix microarray containing 28,869 well-annotated genes revealed that, among the 3412 genes changed more than 1.5-fold by Cr(VI) treatment, changes of 2404 genes (70%) were inhibited by pretreatment of EGCG. Real-time PCR confirmed the induction of 3 genes involved in cell death and apoptosis by Cr(VI), which was eliminated by EGCG. In contrast, Cr(VI) reduced the expression of 3 genes related to cellular defense, and this reduction was inhibited by EGCG. Our results indicate that EGCG protects BEAS-2B cells from Cr(VI)-induced cytotoxicity presumably by scavenging ROS and modulating a subset of genes. EGCG, therefore, might serve as a potential chemopreventive agent against Cr(VI) carcinogenesis.
PubMed ID: 22079256
MeSH Terms: Antioxidants/administration & dosage; Antioxidants/pharmacology*; Apoptosis/drug effects; Bronchi/cytology; Bronchi/drug effects; Bronchi/pathology; Carcinogens, Environmental/toxicity*; Catechin/administration & dosage; Catechin/analogs & derivatives*; Catechin/pharmacology; Chromium/toxicity*; Dose-Response Relationship, Drug; Epithelial Cells/drug effects; Epithelial Cells/pathology; Free Radical Scavengers/administration & dosage; Free Radical Scavengers/pharmacology; Gene Expression Regulation/drug effects; Humans; Microscopy, Fluorescence; Oligonucleotide Array Sequence Analysis; Polymerase Chain Reaction; Reactive Oxygen Species/metabolism*