School of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
Cells. 2024 Oct 3;13(19):1648. doi: 10.3390/cells13191648.
Control of oxidation/antioxidation homeostasis is important for cellular protective functions, and disruption of the antioxidation balance by exogenous and endogenous ligands can lead to profound pathological consequences of cancerous commitment within cells. Although cancers are sensitive to antioxidation drugs, these drugs are sometimes associated with problems including tumor resistance or dose-limiting toxicity in host animals and patients. These problems are often caused by the imbalance between the levels of oxidative stress-induced reactive oxygen species (ROS) and the redox efficacy of antioxidants. Increased ROS levels, because of abnormal function, including metabolic abnormality and signaling aberrations, can promote tumorigenesis and the progression of malignancy, which are generated by genome mutations and activation of proto-oncogene signaling. This hypothesis is supported by various experiments showing that the balance of oxidative stress and redox control is important for cancer therapy. Although many antioxidant drugs exhibit therapeutic potential, there is a heterogeneity of antioxidation functions, including cell growth, cell survival, invasion abilities, and tumor formation, as well as the expression of marker genes including tumor suppressor proteins, cell cycle regulators, nuclear factor erythroid 2-related factor 2, and Jun dimerization protein 2; their effectiveness in cancer remains unproven. Here, we summarize the rationale for the use of antioxidative drugs in preclinical and clinical antioxidant therapy of cancer, and recent advances in this area using cancer cells and their organoids, including the targeting of ROS homeostasis.
氧化/抗氧化平衡的控制对于细胞的保护功能至关重要，外源性和内源性配体对抗氧化平衡的破坏可导致细胞内癌变的深刻病理后果。虽然癌症对抗氧化药物敏感，但这些药物有时会引起一些问题，包括肿瘤耐药或宿主动物和患者的剂量限制毒性。这些问题通常是由氧化应激诱导的活性氧（ROS）水平与抗氧化剂的氧化还原效力之间的不平衡引起的。ROS 水平的增加，由于代谢异常和信号异常等异常功能，可以促进肿瘤发生和恶性进展，这是由基因突变和原癌基因信号的激活引起的。这一假说得到了各种实验的支持，这些实验表明氧化应激和氧化还原控制的平衡对癌症治疗很重要。尽管许多抗氧化药物表现出治疗潜力，但抗氧化功能存在异质性，包括细胞生长、细胞存活、侵袭能力和肿瘤形成，以及肿瘤抑制蛋白、细胞周期调节剂、核因子红细胞 2 相关因子 2 和 Jun 二聚化蛋白 2 等标记基因的表达；它们在癌症中的有效性尚未得到证实。在这里，我们总结了在癌症的临床前和临床抗氧化治疗中使用抗氧化药物的基本原理，以及该领域最近在使用癌细胞及其类器官方面的进展，包括 ROS 平衡的靶向治疗。
