title: No protective effect of curcumin on hydrogen peroxide-induced cytotoxicity in HepG2 cells.
abstract: Scavenging of intracellular reactive oxygen species (ROS) is one of the potential mechanisms contributing to the protective effects of many antioxidants. Curcumin, a natural product, is an effective ROS scavenger. However, the role of its ROS scavenging ability in its cytoprotective action remains to be clarified. Herein, the protective effects of curcumin on hydrogen peroxide (H₂O₂)- and tert-butyl hydroperoxide-induced ROS formation and HepG2 cell injury were determined. HepG2 cells were pretreated with curcumin for 30 min and then treated with H₂O₂ (500 μM) or tert-butyl hydroperoxide (200 μM) for 24 h. Curcumin pretreatment dramatically decreased H₂O₂- and tert-butyl hydroperoxide-induced ROS production, but failed to suppress cytotoxicity of those compounds. H₂O₂ induced decreases in mitochondrial membrane potential (ΔΨm) and increases in DNA fragmentation could not be reversed by curcumin. Furthermore, curcumin enhanced expression of H₂O₂-induced pro-apoptotic protein Bax expression and inhibited expression of anti-apoptotic proteins Bcl-2 and Bcl-xL. In addition, curcumin significantly decreased p38MAPK and phospho-CDC-2 protein expression and increased phospho-p38MAPK, p42/44MAPK, and phospho-p42/44MAPK protein expression. These results suggest that short pretreatment and subsequent longer co-treatment of low concentrations of curcumin showed no obvious protective effect on H₂O₂-induced HepG₂ cell injury.
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Macau 999078, China. xpchen@umac.mo
authors.forename: Xiuping
authors.initials: X
authors.lastname: Chen
authors.forename: Zhangfeng
authors.initials: Z
authors.lastname: Zhong
authors.forename: Zengtao
authors.initials: Z
authors.lastname: Xu
authors.forename: Lidian
authors.initials: L
authors.lastname: Chen
authors.forename: Yitao
authors.initials: Y
authors.lastname: Wang
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010766:Phosphorylation; D017382:Reactive Oxygen Species / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D020122:tert-Butylhydroperoxide / Q000633:toxicity
chemical_list: D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D020122:tert-Butylhydroperoxide; D006861:Hydrogen Peroxide; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D003474:Curcumin