title: The Green Tea Component (-)-Epigallocatechin-3-Gallate Sensitizes Primary Endothelial Cells to Arsenite-Induced Apoptosis by Decreasing c-Jun N-Terminal Kinase-Mediated Catalase Activity.
abstract: The green tea component (-)-epigallocatechin-3-gallate (EGCG) has been shown to sensitize many different types of cancer cells to anticancer drug-induced apoptosis, although it protects against non-cancerous primary cells against toxicity from certain conditions such as exposure to arsenic (As) or ultraviolet irradiation. Here, we found that EGCG promotes As-induced toxicity of primary-cultured bovine aortic endothelial cells (BAEC) at doses in which treatment with each chemical alone had no such effect. Increased cell toxicity was accompanied by an increased condensed chromatin pattern and fragmented nuclei, cleaved poly(ADP-ribose) polymerase (PARP), activity of the pro-apoptotic enzymes caspases 3, 8 and 9, and Bax translocation into mitochondria, suggesting the involvement of an apoptotic signaling pathway. Fluorescence activated cell sorting analysis revealed that compared with EGCG or As alone, combined EGCG and As (EGCG/As) treatment significantly induced production of reactive oxygen species (ROS), which was accompanied by decreased catalase activity and increased lipid peroxidation. Pretreatment with N-acetyl-L-cysteine or catalase reversed EGCG/As-induced caspase activation and EC toxicity. EGCG/As also increased the phosphorylation of c-Jun N-terminal kinase (JNK), which was not reversed by catalase. However, pretreatment with the JNK inhibitor SP600125 reversed all of the observed effects of EGCG/As, suggesting that JNK may be the most upstream protein examined in this study. Finally, we also found that all the observed effects by EGCG/As are true for other types of EC tested. In conclusion, this is firstly to show that EGCG sensitizes non-cancerous EC to As-induced toxicity through ROS-mediated apoptosis, which was attributed at least in part to a JNK-activated decrease in catalase activity.
authors.affiliation: Department of Molecular Medicine, Ewha Womans University School of medicine, Seoul, South Korea; Department of Radiation Oncology, College of Medicine, Yonsei University, Seoul, South Korea.
authors.forename: Jee-Youn
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Department of Molecular Medicine, Ewha Womans University School of medicine, Seoul, South Korea; Department of Nanobiomedical Science & BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, Chungnam, South Korea.
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Choi
authors.affiliation: Department of Molecular Medicine, Ewha Womans University School of medicine, Seoul, South Korea.
authors.forename: Hyeon-Ju
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Molecular Medicine, Ewha Womans University School of medicine, Seoul, South Korea.
authors.forename: Catherine Jeonghae
authors.initials: CJ
authors.lastname: Byun
authors.affiliation: Department of Molecular Medicine, Ewha Womans University School of medicine, Seoul, South Korea.
authors.forename: Jung-Hyun
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Pathology, College of Medicine, Kyung Hee University, Seoul, South Korea.
authors.forename: Jae Hoon
authors.initials: JH
authors.lastname: Park
authors.affiliation: Biosafety Research Institute and College of Veterinary Medicine, Chonbuk National University, Jeonju, Chonbuk, South Korea.
authors.forename: Ho-Seong
authors.initials: HS
authors.lastname: Cho
authors.affiliation: Department of Biology, College of Natural Sciences, Chungbuk National University, Cheongju, South Korea.
authors.forename: Sung-Jin
authors.initials: SJ
authors.lastname: Cho
authors.affiliation: Department of Nanobiomedical Science & BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, Chungnam, South Korea; Department of Pharmacology, College of Pharmacy, Dankook University, Cheonan, Chungnam, South Korea.
authors.forename: Sangmee Ahn
authors.initials: SA
authors.lastname: Jo
authors.affiliation: Department of Molecular Medicine, Ewha Womans University School of medicine, Seoul, South Korea.
authors.forename: Inho
authors.initials: I
authors.lastname: Jo
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001011:Aorta / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D018053:Arsenites / Q000494:pharmacology*; D015153:Blotting, Western; D002374:Catalase / Q000378:metabolism*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002417:Cattle; D002478:Cells, Cultured; D004351:Drug Resistance / Q000187:drug effects; D004357:Drug Synergism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D006801:Humans; D007124:Immunoenzyme Techniques; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D010084:Oxidation-Reduction; D010766:Phosphorylation / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013662:Tea / Q000737:chemistry*; D013723:Teratogens / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D018053:Arsenites; D017382:Reactive Oxygen Species; D013662:Tea; D013723:Teratogens; D002392:Catechin; C045651:epigallocatechin gallate; D002374:Catalase; D048031:JNK Mitogen-Activated Protein Kinases; C015001:arsenite