title: Tumor cell-protective catalase as a novel target for rational therapeutic approaches based on specific intercellular ROS signaling.
abstract: Reactive oxygen species (ROS) exhibit procarcinogenic effects at multiple stages during multistep oncogenesis. As a hallmark of the transformed state, extracellular superoxide anions generated by NADPH oxidase1 (NOX1) are centrally involved in the control of the transformed state. These pro-carcinogenic effects of ROS are counterbalanced by specific ROS-dependent apoptosis induction in malignant cells, based on four interconnected signaling pathways. Tumor progression selects for a phenotype characterized by resistance to ROS-dependent apoptotic signaling. Resistance is based on membrane-associated catalase in tumor cells, which therefore represents a promising and unique target for specific tumor therapy. Novel approache, developed in vitro, utilize antibody-mediated inhibition of catalase or ROS-driven singlet oxygen generation and subsequent inactivation of tumor cell catalase as initial steps. As a consecutive step, malignant cell-generated superoxide anions then drive apoptotic signaling with high selectivity for malignant cells. We propose to translate this complex but well-established ROS-dependent signaling chemistry into novel approaches for experimental therapy in vivo.
authors: Abteilung Virologie, Institut für Medizinische Mikrobiologie und Hygiene, Hermann-Herder Strasse 11, D-79104 Freiburg, Germany. georg.bauer@uniklinik-freiburg.de
authors: Georg
authors: G
authors: Bauer
mesh_terms: D002374:Catalase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods*; D009369:Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000517:prevention & control*; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D002374:Catalase