High concentrations of ascorbic acid induces apoptosis of human gastric cancer cell by p38-MAP kinase-dependent up-regulation of transferrin receptor

被引:34
作者
Ha, Yu Mi
Park, Min Kyu
Kim, Hye Jung
Seo, Han Geuk
Lee, Jae Heun
Chang, Ki Churl [1 ]
机构
[1] Gyeongsang Natl Univ, Sch Med, Dept Pharmacol, Jinju 660751, South Korea
关键词
Apoptosis; Ascorbic acid; Transferrin receptor; p38-MAPK; Hydrogen peroxide; HYDROGEN-PEROXIDE; OXIDATIVE STRESS; VITAMIN-C; IRON UPTAKE; ENDOTHELIAL-CELLS; RADICAL INTENSITY; DOWN-REGULATION; CULTURE-MEDIUM; IN-VITRO; MAINTENANCE;
D O I
10.1016/j.canlet.2008.11.020
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
We investigated the molecular mechanism by which ascorbic acid (AA) induces apoptosis in human gastric cancer cells, AGS cells. High concentration (more than 5 mM) 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. H2O2 increased TfR expression in AGS cells. Taken together, we concluded that high concentration of AA, through H2O2, induces apoptosis of AGS cells by p38-MAPK-dependent upregulation of TfR. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:48 / 54
页数:7
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