Hatem Elie, El Banna Nadine, Huang Meng-Er
1 CNRS UMR3348, Institut Curie, PSL Research University , Orsay, France .
2 CNRS UMR3348, Université Paris Sud, Université Paris-Saclay , Orsay, France .
Antioxid Redox Signal. 2017 Nov 20;27(15):1217-1234. doi: 10.1089/ars.2017.7134. Epub 2017 Jun 26.
Glutathione is the most abundant antioxidant molecule in living organisms and has multiple functions. Intracellular glutathione homeostasis, through its synthesis, consumption, and degradation, is an intricately balanced process. Glutathione levels are often high in tumor cells before treatment, and there is a strong correlation between elevated levels of intracellular glutathione/sustained glutathione-mediated redox activity and resistance to pro-oxidant anticancer therapy. Recent Advances: Ample evidence demonstrates that glutathione and glutathione-based systems are particularly relevant in cancer initiation, progression, and the development of anticancer drug resistance.
This review highlights the multifaceted roles of glutathione and glutathione-based systems in carcinogenesis, anticancer drug resistance, and clinical applications.
The evidence summarized here underscores the important role played by glutathione and the glutathione-based systems in carcinogenesis and anticancer drug resistance. Future studies should address mechanistic questions regarding the distinct roles of glutathione in different stages of cancer development and cancer cell death. It will be important to study how metabolic alterations in cancer cells can influence glutathione homeostasis. Sensitive approaches to monitor glutathione dynamics in subcellular compartments will be an indispensible step. Therapeutic perspectives should focus on mechanism-based rational drug combinations that are directed against multiple redox targets using effective, specific, and clinically safe inhibitors. This new strategy is expected to produce a synergistic effect, prevent drug resistance, and diminish doses of single drugs. Antioxid. Redox Signal. 27, 1217-1234.
谷胱甘肽是生物体内最丰富的抗氧化分子，具有多种功能。细胞内谷胱甘肽通过其合成、消耗和降解实现的稳态是一个复杂的平衡过程。在治疗前，肿瘤细胞中的谷胱甘肽水平通常较高，细胞内谷胱甘肽水平升高/持续的谷胱甘肽介导的氧化还原活性与对促氧化抗癌治疗的耐药性之间存在很强的相关性。最新进展：大量证据表明，谷胱甘肽和基于谷胱甘肽的系统在癌症发生、发展和抗癌药物耐药性的形成中尤为重要。
本综述强调了谷胱甘肽和基于谷胱甘肽的系统在致癌作用、抗癌药物耐药性及临床应用方面的多方面作用。
此处总结的证据强调了谷胱甘肽和基于谷胱甘肽的系统在致癌作用和抗癌药物耐药性中所起的重要作用。未来的研究应解决有关谷胱甘肽在癌症发展和癌细胞死亡不同阶段的不同作用的机制问题。研究癌细胞中的代谢改变如何影响谷胱甘肽稳态将很重要。监测亚细胞区室中谷胱甘肽动态的灵敏方法将是必不可少的一步。治疗前景应聚焦于基于机制的合理药物组合，使用有效、特异且临床安全的抑制剂针对多个氧化还原靶点。这种新策略有望产生协同效应，预防耐药性，并减少单一药物的剂量。《抗氧化. 氧化还原信号》27, 1217 - 1234。
