Battelli Maria Giulia, Polito Letizia, Bortolotti Massimo, Bolognesi Andrea
Department of Experimental, Diagnostic and Specialty Medicine - DIMES, Alma Mater Studiorum - University of Bologna, General Pathology Unit, Via S. Giacomo 14, 40126, Bologna, Italy.
Cancer Med. 2016 Mar;5(3):546-57. doi: 10.1002/cam4.601. Epub 2015 Dec 21.
Human xanthine oxidoreductase (XOR) catalyzes the last two steps of purine catabolism and is present in two interconvertible forms, which may utilize O2 or NAD(+) as electron acceptors. In addition to uric acid, XOR products may comprise reactive oxygen and nitrogen species that have many biologic effects, including inflammation, endothelial dysfunction, and cytotoxicity, as well as mutagenesis and induction of proliferation. XOR is strictly modulated at the transcriptional and post-translational levels, and its expression and activity are highly variable in cancer. Xanthine oxidoreductase (XOR) expression has been negatively associated with a high malignity grade and a worse prognosis in neoplasms of the breast, liver, gastrointestinal tract, and kidney, which normally express a high level of XOR protein. However, the level of XOR expression may be associated with a worse outcome in cancer of low XOR-expressing cells, in relation to the inflammatory response elicited through the tissue damage induced by tumor growth. Xanthine oxidoreductase (XOR) has been implicated in the process of oncogenesis either directly because it is able to catalyze the metabolic activation of carcinogenic substances or indirectly through the action of XOR-derived reactive oxygen and nitrogen species. The role of uric acid is characterized by both oxidant and antioxidant action; thus, it is still debatable whether control of uricemia may be helpful to improve the outcomes of tumor illness.
人黄嘌呤氧化还原酶（XOR）催化嘌呤分解代谢的最后两步，以两种可相互转化的形式存在，这两种形式可利用O2或NAD(+)作为电子受体。除尿酸外，XOR的产物可能包括具有多种生物学效应的活性氧和氮物质，这些效应包括炎症、内皮功能障碍和细胞毒性，以及诱变和增殖诱导。XOR在转录和翻译后水平受到严格调控，其表达和活性在癌症中高度可变。黄嘌呤氧化还原酶（XOR）的表达与乳腺癌、肝癌、胃肠道癌和肾癌的高恶性分级及较差预后呈负相关，这些肿瘤通常表达高水平的XOR蛋白。然而，就肿瘤生长诱导的组织损伤引发的炎症反应而言，XOR表达水平可能与低XOR表达细胞的癌症预后较差有关。黄嘌呤氧化还原酶（XOR）直接参与肿瘤发生过程，因为它能够催化致癌物质的代谢活化，或通过XOR衍生的活性氧和氮物质间接参与。尿酸的作用兼具氧化和抗氧化作用；因此，控制血尿酸水平是否有助于改善肿瘤疾病的预后仍存在争议。
