Glutathione (GSH) is the most abundant non-protein thiol present at millimolar concentrations in mammalian tissues. As an important intracellular antioxidant, it acts as a regulator of cellular redox state protecting cells from damage caused by lipid peroxides, reactive oxygen and nitrogen species, and xenobiotics. Recent studies have highlighted the importance of GSH in key signal transduction reactions as a controller of cell differentiation, proliferation, apoptosis, ferroptosis and immune function. Molecular changes in the GSH antioxidant system and disturbances in GSH homeostasis have been implicated in tumor initiation, progression, and treatment response. Hence, GSH has both protective and pathogenic roles. Although in healthy cells it is crucial for the removal and detoxification of carcinogens, elevated GSH levels in tumor cells are associated with tumor progression and increased resistance to chemotherapeutic drugs. Recently, several novel therapies have been developed to target the GSH antioxidant system in tumors as a means for increased response and decreased drug resistance. In this comprehensive review we explore mechanisms of GSH functionalities and different therapeutic approaches that either target GSH directly, indirectly or use GSH-based prodrugs. Consideration is also given to the computational methods used to describe GSH related processes for in silico testing of treatment effects.

中文翻译：

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谷胱甘肽在癌症中的作用：从机制到治疗

谷胱甘肽 (GSH) 是哺乳动物组织中以毫摩尔浓度存在的最丰富的非蛋白质硫醇。作为一种重要的细胞内抗氧化剂，它充当细胞氧化还原状态的调节剂，保护细胞免受脂质过氧化物、活性氧和氮物质以及外源性物质的损害。最近的研究强调了 GSH 在关键信号转导反应中作为细胞分化、增殖、凋亡、铁死亡和免疫功能的控制器的重要性。GSH 抗氧化系统的分子变化和 GSH 稳态的紊乱与肿瘤的发生、进展和治疗反应有关。因此，GSH 具有保护和致病作用。虽然在健康细胞中，它对于致癌物的去除和解毒至关重要，肿瘤细胞中 GSH 水平升高与肿瘤进展和对化疗药物的耐药性增加有关。最近，已经开发出几种新疗法以靶向肿瘤中的 GSH 抗氧化系统，作为增加反应和降低耐药性的手段。在这篇综合综述中，我们探讨了 GSH 功能的机制以及直接、间接靶向 GSH 或使用基于 GSH 的前药的不同治疗方法。还考虑了用于描述处理效果的计算机测试中 GSH 相关过程的计算方法。在这篇综合综述中，我们探讨了 GSH 功能的机制以及直接、间接靶向 GSH 或使用基于 GSH 的前药的不同治疗方法。还考虑了用于描述处理效果的计算机测试中 GSH 相关过程的计算方法。在这篇综合综述中，我们探讨了 GSH 功能的机制以及直接、间接靶向 GSH 或使用基于 GSH 的前药的不同治疗方法。还考虑了用于描述处理效果的计算机测试中 GSH 相关过程的计算方法。