title: High concentrations of ascorbic acid induces apoptosis of human gastric cancer cell by p38-MAP kinase-dependent up-regulation of transferrin receptor.
abstract: We investigated the molecular mechanism by which ascorbic acid (AA) induces apoptosis in human gastric cancer cells, AGS cells. High concentration (more than 5mM) of AA increased cellular iron uptake by increasing transferrin receptor (TfR) expression and induced AGS cell apoptosis which was inhibited by catalase. Interestingly, p38 mitogen-activated protein kinase (MAPK) inhibitor inhibited the upregulation of TfR and increased cell survival by AA. TfR-siRNA-transfected cells reduced apoptosis by AA. H(2)O(2) increased TfR expression in AGS cells. Taken together, we concluded that high concentration of AA, through H(2)O(2), induces apoptosis of AGS cells by p38-MAPK-dependent upregulation of TfR.
authors.affiliation: Department of Pharmacology, School of Medicine and Institute of Health Sciences, Gyeongsang National University, Jinju, Republic of Korea.
authors.forename: Yu Mi
authors.initials: YM
authors.lastname: Ha
authors.forename: Min Kyu
authors.initials: MK
authors.lastname: Park
authors.forename: Hye Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Han Geuk
authors.initials: HG
authors.lastname: Seo
authors.forename: Jae Heun
authors.initials: JH
authors.lastname: Lee
authors.forename: Ki Churl
authors.initials: KC
authors.lastname: Chang
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001205:Ascorbic Acid / Q000494:pharmacology*; D002374:Catalase / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D053960:DNA Breaks; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D007501:Iron / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D011725:Pyridines / Q000494:pharmacology; D011990:Receptors, Transferrin / Q000502:physiology*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology*
chemical_list: D007093:Imidazoles; D019253:Proto-Oncogene Proteins c-bcl-2; D011725:Pyridines; D011990:Receptors, Transferrin; D006861:Hydrogen Peroxide; D007501:Iron; D002374:Catalase; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580; D001205:Ascorbic Acid