PDF(Pubmed)
Abstract：
The intracellular redox homeostasis is a dynamic balancing system between the levels of free radical species and antioxidant enzymes and small molecules at the core of cellular defense mechanisms. The thioredoxin (Trx) system is an important detoxification system regulating the redox milieu. This system is one of the key regulators of cells\' proliferative potential as well, through the reduction of key proteins. Increased oxidative stress characterizes highly proliferative, metabolically hyperactive cancer cells, which are forced to mobilize antioxidant enzymes to balance the increase in free radical concentration and prevent irreversible damage and cell death. Components of the Trx system are involved in high-rate proliferation and activation of pro-survival mechanisms in cancer cells, particularly those facing increased oxidative stress. This review addresses the importance of the targetable redox-regulating Trx system in tumor progression, as well as in detoxification and protection of cancer cells from oxidative stress and drug-induced cytotoxicity. It also discusses the cancer cells\' counteracting mechanisms to the Trx system inhibition and presents several inhibitors of the Trx system as prospective candidates for cytostatics\' adjuvants. This manuscript further emphasizes the importance of developing novel multitarget therapies encompassing the Trx system inhibition to overcome cancer treatment limitations.
摘要：
细胞内氧化还原稳态是细胞防御机制核心的自由基种类和抗氧化酶和小分子水平之间的动态平衡系统。硫氧还蛋白（Trx）系统是调节氧化还原环境的重要解毒系统。该系统也是细胞增殖潜能的关键调节因子之一，通过减少关键蛋白质。增加的氧化应激表征高度增殖，代谢过度活跃的癌细胞，它们被迫动员抗氧化酶来平衡自由基浓度的增加，防止不可逆的损伤和细胞死亡。Trx系统的成分参与癌细胞的高速率增殖和促存活机制的激活，特别是那些面临增加的氧化应激。这篇综述阐述了靶向氧化还原调节Trx系统在肿瘤进展中的重要性。以及解毒和保护癌细胞免受氧化应激和药物诱导的细胞毒性。它还讨论了癌细胞对抗Trx系统抑制的机制，并提出了Trx系统的几种抑制剂作为细胞抑制剂佐剂的潜在候选物。该手稿进一步强调了开发包含Trx系统抑制的新型多靶标疗法以克服癌症治疗限制的重要性。
