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	Katrin Scheit, Georg Bauer
Journal	Anticancer research (Anticancer Res) Vol. 34 Issue 10 Pg. 5337-50 (Oct 2014) ISSN: 1791-7530 [Electronic] Greece
PMID	25275027 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright	Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.
Chemical References	Anthocyanins Enzyme Inhibitors RNA, Small Interfering Reactive Oxygen Species Nitric Oxide cyanidin Catalase Oxygenases nitric oxide dioxygenase Caspase 8 Salicylic Acid NG-Nitroarginine Methyl Ester
Topics	Anthocyanins (pharmacology) Apoptosis (drug effects, genetics) Caspase 8 (metabolism) Catalase (antagonists & inhibitors, metabolism) Cell Line, Tumor Dose-Response Relationship, Drug Drug Synergism Enzyme Inhibitors (pharmacology) Humans NG-Nitroarginine Methyl Ester (pharmacology) Neoplasms (genetics, metabolism) Nitric Oxide (metabolism) Oxygenases (antagonists & inhibitors, metabolism) RNA Interference RNA, Small Interfering Reactive Oxygen Species (metabolism) Salicylic Acid (pharmacology)

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