title: Epigallocatechin-3-gallate (EGCG) protects against chromate-induced toxicity in vitro.
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.
authors.affiliation: Department of Environmental Medicine, New York University School of Medicine, Tuxedo, NY 10987, USA.
authors.forename: Fen
authors.initials: F
authors.lastname: Wu
authors.forename: Hong
authors.initials: H
authors.lastname: Sun
authors.forename: Thomas
authors.initials: T
authors.lastname: Kluz
authors.forename: Hailey A
authors.initials: HA
authors.lastname: Clancy
authors.forename: Kathrin
authors.initials: K
authors.lastname: Kiok
authors.forename: Max
authors.initials: M
authors.lastname: Costa
mesh_terms: D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001980:Bronchi / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D002274:Carcinogens, Environmental / Q000633:toxicity*; D002392:Catechin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D002857:Chromium / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology; D016166:Free Radical Scavengers / Q000008:administration & dosage / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008856:Microscopy, Fluorescence; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D002274:Carcinogens, Environmental; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D002857:Chromium; C074702:chromium hexavalent ion; D002392:Catechin; C045651:epigallocatechin gallate
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