Abteilung Virologie, Institut für Medizinische Mikrobiologie und Hygiene, Hermann-Herder Strasse 11, D-79104 Freiburg, Germany.
Anticancer Res. 2012 Jul;32(7):2599-624.
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.
活性氧 (ROS) 在多步骤致癌作用的多个阶段表现出致癌作用。作为转化状态的标志，NADPH 氧化酶 1 (NOX1) 产生的细胞外超氧阴离子在控制转化状态中起着核心作用。这些 ROS 的促癌作用被恶性细胞中特定的 ROS 依赖性细胞凋亡诱导所平衡，基于四个相互关联的信号通路。肿瘤进展选择了一种以对 ROS 依赖性细胞凋亡信号具有抗性为特征的表型。抗性基于肿瘤细胞中的膜结合过氧化氢酶，因此它代表了一种有前途且独特的特异性肿瘤治疗靶点。新的方法在体外开发，利用抗体介导的过氧化氢酶抑制或 ROS 驱动的单线态氧生成以及随后的肿瘤细胞过氧化氢酶失活作为初始步骤。作为连续的步骤，恶性细胞产生的超氧阴离子然后驱动具有高选择性的凋亡信号，针对恶性细胞。我们建议将这种复杂但成熟的 ROS 依赖性信号化学转化为体内实验治疗的新方法。
