Department of Pharmacology, Biological Sciences Sector, Federal University of Paraná, Curitiba, PR, Brazil.
Department of Pharmacology, Biological Sciences Sector, Federal University of Paraná, Curitiba, PR, Brazil.
Crit Rev Oncol Hematol. 2018 Aug;128:43-57. doi: 10.1016/j.critrevonc.2018.05.014. Epub 2018 May 21.
Glutathione (GSH) is one of the most important defenses against oxidative stress through the fine-tuned regulation of redox homeostasis. Glutathione is also involved in many metabolic processes and is important for the regulation of cell survival, proliferation, and death. Furthermore, GSH and the enzymes that are involved in its biosynthesis, catabolism, and detoxification (e.g., disulfide-oxidized glutathione, glutathione S-transferase, glutathione peroxidase, glutathione reductase, and γ-glutamyltranspetidase) play an important role in several diseases, including cancer. In cancer cells, these enzymes protect the tumor microenvironment against oxidative stress and cell death and are important for tumor growth and development. Thus, the GSH system is an important tool for investigating new pharmacological approaches for cancer treatment. Several preclinical models of solid tumors are available for this purpose. This review summarizes and discusses the regulation and dysregulation of GSH and its related enzymes in different models of solid tumors, and potential treatments that target the GSH system.
谷胱甘肽（GSH）是通过精细调节氧化还原平衡来抵御氧化应激的最重要防御机制之一。谷胱甘肽还参与许多代谢过程，对于细胞存活、增殖和死亡的调节也很重要。此外，GSH 及其生物合成、分解代谢和解毒（例如，二硫氧化谷胱甘肽、谷胱甘肽 S-转移酶、谷胱甘肽过氧化物酶、谷胱甘肽还原酶和γ-谷氨酰转肽酶）所涉及的酶在包括癌症在内的几种疾病中发挥着重要作用。在癌细胞中，这些酶可以保护肿瘤微环境免受氧化应激和细胞死亡的影响，对于肿瘤的生长和发展也很重要。因此，GSH 系统是研究癌症治疗新的药理学方法的重要工具。为此，已经有几种实体瘤的临床前模型可用。本文综述并讨论了不同实体瘤模型中 GSH 及其相关酶的调节和失调，以及针对 GSH 系统的潜在治疗方法。
