title: Synergistic effects between catalase inhibitors and modulators of nitric oxide metabolism on tumor cell apoptosis.
abstract: Inhibitors of catalase (such as ascorbate, methyldopa, salicylic acid and neutralizing antibodies) synergize with modulators of nitric oxide (NO) metabolism (such as arginine, arginase inhibitor, NO synthase-inducing interferons and NO dioxygenase inhibitors) in the singlet oxygen-mediated inactivation of tumor cell protective catalase. This is followed by reactive oxygen species (ROS)-dependent apoptosis induction. TGF-beta, NADPH oxidase-1, NO synthase, dual oxidase-1 and caspase-9 are characterized as essential catalysts in this process. The FAS receptor and caspase-8 are required for amplification of ROS signaling triggered by individual compounds, but are dispensable when the synergistic effect is established. Our findings explain the antitumor effects of catalase inhibitors and of compounds that target NO metabolism, as well as their synergy. These data may have an impact on epidemiological studies related to secondary plant compounds and open new perspectives for the establishment of novel antitumor drugs and for the improvement of established chemotherapeutics.
authors.affiliation: Institute of Virology, Department of Medical Microbiology and Hygiene, University Medical Center, Freiburg, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Scheit
authors.affiliation: Institute of Virology, Department of Medical Microbiology and Hygiene, University Medical Center, Freiburg, Germany georg.bauer@uniklinik-freiburg.de.
authors.forename: Georg
authors.initials: G
authors.lastname: Bauer
mesh_terms: D000872:Anthocyanins / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D053181:Caspase 8 / Q000378:metabolism; D002374:Catalase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D010105:Oxygenases / Q000037:antagonists & inhibitors / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species / Q000378:metabolism; D020156:Salicylic Acid / Q000494:pharmacology
chemical_list: D000872:Anthocyanins; D004791:Enzyme Inhibitors; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; C017154:cyanidin; D002374:Catalase; D010105:Oxygenases; C114415:nitric oxide dioxygenase; D053181:Caspase 8; D020156:Salicylic Acid; D019331:NG-Nitroarginine Methyl Ester
keywords: Apoptosis; ROS signaling; ascorbic acid; catalase; interferon; nitric oxide; nitric oxide dioxygenase; salicylic acid; singlet oxygen