title: Quercetin 3-O-methyl ether protects FL83B cells from copper induced oxidative stress through the PI3K/Akt and MAPK/Erk pathway.
abstract: Quercetin is a bioflavonoid that exhibits several biological functions in vitro and in vivo. Quercetin 3-O-methyl ether (Q3) is a natural product reported to have pharmaceutical activities, including antioxidative and anticancer activities. However, little is known about the mechanism by which it protects cells from oxidative stress. This study was designed to investigate the mechanisms by which Q3 protects against Cu(2+)-induced cytotoxicity. Exposure to Cu(2+) resulted in the death of mouse liver FL83B cells, characterized by apparent apoptotic features, including DNA fragmentation and increased nuclear condensation. Q3 markedly suppressed Cu(2+)-induced apoptosis and mitochondrial dysfunction, characterized by reduced mitochondrial membrane potential, caspase-3 activation, and PARP cleavage, in Cu(2+)-exposed cells. The involvement of PI3K, Akt, Erk, FOXO3A, and Mn-superoxide dismutase (MnSOD) was shown to be critical to the survival of Q3-treated FL83B cells. The liver of both larval and adult zebrafish showed severe damage after exposure to Cu(2+) at a concentration of 5μM. Hepatic damage induced by Cu(2+) was reduced by cotreatment with Q3. Survival of Cu(2+)-exposed larval zebrafish was significantly increased by cotreatment with 15μM Q3. Our results indicated that Cu(2+)-induced apoptosis in FL83B cells occurred via the generation of ROS, upregulation and phosphorylation of Erk, overexpression of 14-3-3, inactivation of Akt, and the downregulation of FOXO3A and MnSOD. Hence, these results also demonstrated that Q3 plays a protective role against oxidative damage in zebrafish liver and remarked the potential of Q3 to be used as an antioxidant for hepatocytes.
authors: Department of Life Sciences, Tzu Chi University, Hualien, Taiwan. lily1001224@gmail.com
authors: Hsiao-Ling
authors: HL
authors: Tseng
authors: Chia-Jung
authors: CJ
authors: Li
authors: Lin-Huang
authors: LH
authors: Huang
authors: Chun-Yao
authors: CY
authors: Chen
authors: Chun-Hao
authors: CH
authors: Tsai
authors: Chun-Nan
authors: CN
authors: Lin
authors: Hsue-Yin
authors: HY
authors: Hsu
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D003300:Copper / Q000633:toxicity*; D053938:DNA Fragmentation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008930:Mitochondria, Liver / Q000187:drug effects / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011794:Quercetin / Q000031:analogs & derivatives* / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D015027:Zebrafish
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; C459210:quercetin 3-O-methyl ether; D003300:Copper; D011794:Quercetin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt