Modulation of intercellular ROS signaling of human tumor cells.
Tumor cells are resistant against apoptosis-inducing intercellular reactive oxygen species (ROS) signaling but can be resensitized by the inhibition of catalase. Hydrogen peroxide exhibits a dual role in the modulation of intercellular ROS signaling. When suboptimal concentrations of the catalase inhibitior 3-aminotriazole (3-AT) are applied, additional exogenous hydrogen peroxide shifts apoptosis induction to its optimum. When hydrogen peroxide is added at optimal concentrations of 3-AT, or when higher concentrations of 3-AT are applied, the subsequent consumption between HOCl and hydrogen peroxide blunts overall apoptosis induction. These supraoptimal conditions can be brought back to the optimum through excess myeloperoxidase (MPO), partial removal of hydrogen peroxide through the catalase mimetic EUK-134 or partial inhibition of NADPH oxidase. Exogenous nitric oxide (NO) interferes with HOCl signaling through consumption of hydrogen peroxide. Site-specific generation of hydroxyl radicals at the cell membrane of tumor cells induces apoptosis, whereas random HOCl-superoxide anion interaction, and ferrous iron-induced Fenton chemistry of HOCl inhibit intercellular ROS signaling.
Bechtel
Wibke
W
Harvard Medical School, BIDMC, Departmentof Matrix Biology, Boston, MA 02215, USA.
Bauer
Georg
G
D000640:Amitrole / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002374:Catalase / Q000037:antagonists & inhibitors; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D006997:Hypochlorous Acid / Q000494:pharmacology; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology
D004791:Enzyme Inhibitors; D017382:Reactive Oxygen Species; D006997:Hypochlorous Acid; D006861:Hydrogen Peroxide; D002374:Catalase; D019255:NADPH Oxidases; D000640:Amitrole