铜锌超氧化物歧化酶（Copper-zinc Superoxide Dismutase，SOD1）是胞内广泛存在的抗氧化酶，催化O2·-歧化为H2O2和O2，维持胞内活性氧物种（ROS）内稳态。癌细胞的生长、增殖都依赖于适度高浓度的H2O2，高表达的SOD1维持癌细胞内较高水平的H2O2和ROS内稳态。抑制癌细胞内SOD1的活性，可以有效调节ROS信号通路，抑制癌细胞的生长、增殖，阻滞癌细胞周期，促进癌细胞凋亡。因此，通过抑制其活性调控癌细胞内ROS信号网络并选择性杀死癌细胞已经成为抗癌药物设计的一个重要方向。本文主要总结了各类SOD1抑制剂，以及SOD1抑制对ROS信号转导的调控，分析了SOD1特异抑制选择性杀死癌细胞的机制。
Copper-zinc superoxide dismutase(SOD1) is an antioxidant metalloenzyme that widely distriutes within a cell, and catalyzes rapid dismutation of superoxide anion(O2·-) into hydrogen peroxide(H2O2) and oxygen(O2) to maintain the homeostasis of intracellular reactive oxygen species(ROS). The growth and proliferation of cancer cells depend on higher concentrations of H2O2, whereas high expression of SOD1 can maintain higher H2O2 levels and ROS homeostasis of cancer cells. SOD1 inhibition effectively regulates ROS signaling pathways in a cancer cell, inhibits cancer cell growth and proliferation, arrests cancer cell cycle, and promotes cancer cell apoptosis. Targeting SOD1 can regulate the ROS signaling network and selectively kill cancer cells. This review summarizes various types of SOD1 inhibitors designed so far, the regulation of ROS signaling transduction by SOD1 inhibition, and the mechanism of specific SOD1 inhibition-mediated apoptosis of cancer cells.
Contents
1 Introduction
2 The structure and function of SOD1
2.1 Structure and catalytic mechanism of SOD1
2.2 Functions of SOD1
3 Regulation of ROS signaling pathways by SOD1
3.1 SOD1 and ROS signaling pathways
3.2 SOD1 and cancer
4 SOD1 inhibition
4.1 Inhibition of SOD1 expression
4.2 SOD1 inhibitors
5 SOD1 inhibition-regulated ROS signaling pathways
6 Conclusion
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