title: Apoptosis/necrosis switch in two different cancer cell lines: influence of benzoquinone- and hydrogen peroxide-induced oxidative stress intensity, and glutathione.
abstract: Depending on the strength of oxidative stress, cells exhibit proliferative, apoptotic or necrotic responses. We have investigated whether the severity of glutathione (GSH) depletion could determine the type of cell death using 1,4-benzoquinone (BQ) and H(2)O(2) in two different tumor cell lines (human mammary gland carcinoma MCF-7 and rat hepatoma H5-6). BQ-treated surviving cells showed an increase in GSH, but no detectable oxidized glutathione (GSSG) nor reactive oxygen species (ROS) augmentation. Alternatively, H(2)O(2) depressed GSH. BQ induced mostly apoptosis, up to 90% cell elimination, while necrosis was prominent in H(2)O(2)-treated cultures. The resistance of BQ-treated cells to necrosis could be due to increased cellular GSH and formation of BQ-GSH conjugates which are less toxic than free BQ, minimal toxicity being provided by GS4-BHQ. This ability of certain cancer cells to tightly keep the apoptotic pathway may have therapeutic applications for oxidation-based drugs.
authors.affiliation: Laboratoire d'Ingénierie Moléculaire et Biochimie Pharmacologique, Université Paul Verlaine-Metz, Institut Jean Barriol FR CNRS 2843, Rue du Général Delestraint, Metz, France.
authors.forename: Mojgan Ghavam
authors.initials: MG
authors.lastname: Baigi
authors.forename: Laurent
authors.initials: L
authors.lastname: Brault
authors.forename: Adrien
authors.initials: A
authors.lastname: Néguesque
authors.forename: Marc
authors.initials: M
authors.lastname: Beley
authors.forename: Rizlaine El
authors.initials: RE
authors.lastname: Hilali
authors.forename: Franck
authors.initials: F
authors.lastname: Gaüzère
authors.forename: Denyse
authors.initials: D
authors.lastname: Bagrel
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D016227:Benzoquinones / Q000494:pharmacology; D001943:Breast Neoplasms / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D005978:Glutathione / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D009336:Necrosis / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats
chemical_list: D016227:Benzoquinones; C004532:quinone; D006861:Hydrogen Peroxide; D005978:Glutathione