Division of Anti-tumor Pharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
University of Chinese Academy of Sciences, Beijing, 100049, China.
Acta Pharmacol Sin. 2022 Jul;43(7):1623-1632. doi: 10.1038/s41401-021-00800-7. Epub 2021 Nov 22.
Xanthine oxidoreductase (XOR) is a critical, rate-limiting enzyme that controls the last two steps of purine catabolism by converting hypoxanthine to xanthine and xanthine to uric acid. It also produces reactive oxygen species (ROS) during the catalytic process. The enzyme is generally recognized as a drug target for the therapy of gout and hyperuricemia. The catalytic products uric acid and ROS act as antioxidants or oxidants, respectively, and are involved in pro/anti-inflammatory actions, which are associated with various disease manifestations, including metabolic syndrome, ischemia reperfusion injury, cardiovascular disorders, and cancer. Recently, extensive efforts have been devoted to understanding the paradoxical roles of XOR in tumor promotion. Here, we summarize the expression of XOR in different types of cancer and decipher the dual roles of XOR in cancer by its enzymatic or nonenzymatic activity to provide an updated understanding of the mechanistic function of XOR in cancer. We also discuss the potential to modulate XOR in cancer therapy.
黄嘌呤氧化还原酶（XOR）是一种关键的限速酶，通过将次黄嘌呤转化为黄嘌呤，再将黄嘌呤转化为尿酸，控制嘌呤分解代谢的最后两步。在催化过程中，它还会产生活性氧物种（ROS）。该酶通常被认为是治疗痛风和高尿酸血症的药物靶点。催化产物尿酸和 ROS 分别作为抗氧化剂或氧化剂，参与促炎/抗炎作用，与多种疾病表现有关，包括代谢综合征、缺血再灌注损伤、心血管疾病和癌症。最近，人们进行了广泛的努力来了解 XOR 在肿瘤促进中的矛盾作用。在这里，我们总结了 XOR 在不同类型癌症中的表达，并通过其酶或非酶活性来破译 XOR 在癌症中的双重作用，以提供对 XOR 在癌症中的机制功能的最新理解。我们还讨论了在癌症治疗中调节 XOR 的潜力。
