Radiation Biology & Health Sciences Division, Bio-science Group, Bhabha Atomic Research Centre, Trombay, Mumbai-400085, India; Homi Bhabha National Institute, Anushaktinagar, Mumbai-400094, India.
Homi Bhabha National Institute, Anushaktinagar, Mumbai-400094, India.
Arch Biochem Biophys. 2021 Jun 15;704:108890. doi: 10.1016/j.abb.2021.108890. Epub 2021 Apr 21.
The survival, functioning and proliferation of mammalian cells are highly dependent on the cellular response and adaptation to changes in their redox environment. Cancer cells often live in an altered redox environment due to aberrant neo-vasculature, metabolic reprogramming and dysregulated proliferation. Thus, redox adaptations are critical for their survival. Glutathione plays an essential role in maintaining redox homeostasis inside the cells by binding to redox-sensitive cysteine residues in proteins by a process called S-glutathionylation. S-Glutathionylation not only protects the labile cysteine residues from oxidation, but also serves as a sensor of redox status, and acts as a signal for stimulation of downstream processes and adaptive responses to ensure redox equilibrium. The present review aims to provide an updated overview of the role of the unique redox adaptations during carcinogenesis and cancer progression, focusing on their dependence on S-glutathionylation of specific redox-sensitive proteins involved in a wide range of processes including signalling, transcription, structural maintenance, mitochondrial functions, apoptosis and protein recycling. We also provide insights into the role of S-glutathionylation in the development of resistance to chemotherapy. Finally, we provide a strong rationale for the development of redox targeting drugs for treatment of refractory/resistant cancers.
哺乳动物细胞的存活、功能和增殖高度依赖于细胞对其氧化还原环境变化的反应和适应。由于异常的新生血管、代谢重编程和失调的增殖，癌细胞通常生活在改变的氧化还原环境中。因此，氧化还原适应对于它们的存活至关重要。谷胱甘肽通过将巯基（Cysteine）残基与蛋白质结合来维持细胞内的氧化还原平衡，这一过程称为 S-谷胱甘肽化。S-谷胱甘肽化不仅可以保护不稳定的半胱氨酸残基免受氧化，还可以作为氧化还原状态的传感器，并作为刺激下游过程和适应反应的信号，以确保氧化还原平衡。本综述旨在提供对致癌和癌症进展过程中独特的氧化还原适应作用的最新概述，重点介绍它们对参与广泛过程（包括信号转导、转录、结构维持、线粒体功能、细胞凋亡和蛋白质回收）的特定氧化还原敏感蛋白的 S-谷胱甘肽化的依赖性。我们还探讨了 S-谷胱甘肽化在化疗耐药性发展中的作用。最后，我们为开发针对氧化还原的药物治疗难治性/耐药性癌症提供了强有力的理论依据。
