title: Baicalein (5,6,7-trihydroxyflavone) reduces oxidative stress-induced DNA damage by upregulating the DNA repair system.
abstract: Oxidative stress caused by reactive oxygen species (ROS) induces DNA base modifications and DNA strand breaks. In this study, the protective effect of baicalein against H(2)O(2)-induced DNA damage was investigated in V79-4 Chinese hamster fibroblast cells. H(2)O(2) treatment increased the levels of intracellular ROS and DNA double-strand breaks (DSBs) and decreased the level of Ku70 protein and the phosphorylation (activation) of DNA-dependent protein kinase catalytic subunit (DNA-PKcs), which are involved in the repair of DSBs by nonhomologous end joining. Baicalein effectively scavenged intracellular ROS induced by H(2)O(2), reduced DSBs, and rescued Ku70 protein level and phosphorylation of DNA-PKcs. In cellular response to DNA base damage, 8-oxoguanine DNA glycosylase 1 (OGG1) plays a vital role in the removal of 8-oxoguanine (8-OxoG), which is formed mainly by oxidative stress. Baicalein significantly decreased the levels of 8-OxoG induced by H(2)O(2), and this correlated with increases in OGG1 promoter activity and OGG1 mRNA and protein expression. The phosphorylated form of Akt kinase, which is a regulator of OGG1, was sharply decreased by H(2)O(2), but was prevented by baicalein. A specific Akt inhibitor abolished the cytoprotective effects of baicalein, suggesting that OGG1 induction by baicalein involves the Akt pathway. In conclusion, baicalein exerted protective effects against DNA damage induced by oxidative stress by activating DNA repair systems and scavenging ROS.
authors.affiliation: School of Medicine and Applied Radiological Science Research Institute, Jeju National University, Jeju, 690-756, Republic of Korea.
authors.forename: Ki Cheon
authors.initials: KC
authors.lastname: Kim
authors.forename: In Kyung
authors.initials: IK
authors.lastname: Lee
authors.forename: Kyoung Ah
authors.initials: KA
authors.lastname: Kang
authors.forename: Hye Sun
authors.initials: HS
authors.lastname: Kim
authors.forename: Sam Sik
authors.initials: SS
authors.lastname: Kang
authors.forename: Jin Won
authors.initials: JW
authors.lastname: Hyun
mesh_terms: D000818:Animals; D034961:Antigens, Nuclear / Q000096:biosynthesis; D002460:Cell Line; D006224:Cricetinae; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects*; D045647:DNA Glycosylases / Q000235:genetics / Q000378:metabolism; D004260:DNA Repair / Q000187:drug effects*; D051747:DNA-Activated Protein Kinase / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D044950:Flavanones / Q000494:pharmacology*; D006147:Guanine / Q000031:analogs & derivatives / Q000096:biosynthesis; D006861:Hydrogen Peroxide / Q000494:pharmacology; D000072200:Ku Autoantigen; D018384:Oxidative Stress / Q000187:drug effects*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; D044950:Flavanones; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C006680:baicalein; C024829:8-hydroxyguanine; D006147:Guanine; D006861:Hydrogen Peroxide; D051747:DNA-Activated Protein Kinase; D051057:Proto-Oncogene Proteins c-akt; D045647:DNA Glycosylases; D000072200:Ku Autoantigen