Department of Pharmacognosy and Ethnopharmacy, Faculty of Pharmaceutical Sciences, Usmanu Danfodiyo University, Sokoto, Nigeria; UPM-MAKNA Cancer Research Lab, Institute of Bioscience, Universiti Putra Malaysia, Malaysia.
UPM-MAKNA Cancer Research Lab, Institute of Bioscience, Universiti Putra Malaysia, Malaysia.
Biomed Pharmacother. 2019 Jan;109:1506-1510. doi: 10.1016/j.biopha.2018.10.200. Epub 2018 Nov 14.
Apoptosis is a series of molecular signalling regulating normal cellular growth and development. Cells resistance to apoptosis, however, leads to uncontrolled proliferation. Research involving cancer cell death is one of the most important targeted areas in the discovery of novel anticancer therapy. There are several biochemical pathways that are liked towards cancer cell death of which, uridine-cytidine kinase 2 (UCK2) was recently linked to cell apoptosis induction. UCK2 is responsible for the phosphorylation of uridine and cytidine to their corresponding monophosphate in a salvage pathway of pyrimidine nucleotides biosynthesis. Cytotoxic ribonucleoside analogues that target UCK2 enzyme activity are currently being investigated in clinical trials useful for cancer treatment. Whilst findings have clearly shown that these antimetabolites inhibit cancer development in clinical settings, they have yet to establish linking cytotoxic nucleoside analogues to cancer cell death. In this present review, we propose the probable molecular crosstalk involving UCK2 protein and cancer cell death through cell cycle arrest and triggering of apoptosis involving proteins, MDM2 and the subsequent activation of p53.
细胞凋亡是一系列调控正常细胞生长和发育的分子信号。然而，细胞对凋亡的抵抗导致了不受控制的增殖。涉及癌细胞死亡的研究是发现新型抗癌疗法的最重要靶向领域之一。有几种生化途径与癌细胞死亡有关，其中，尿苷-胞苷激酶 2 (UCK2) 最近与细胞凋亡诱导有关。UCK2 负责将尿苷和胞苷磷酸化为嘧啶核苷酸生物合成补救途径中的相应单磷酸。目前正在临床试验中研究针对 UCK2 酶活性的细胞毒性核苷类似物，这些类似物可用于癌症治疗。虽然研究结果清楚地表明，这些抗代谢物在临床环境中抑制癌症的发展，但它们尚未将细胞毒性核苷类似物与癌细胞死亡联系起来。在本综述中，我们提出了 UCK2 蛋白与癌症细胞死亡之间可能的分子相互作用，包括细胞周期停滞和通过蛋白质 MDM2 触发凋亡，以及随后 p53 的激活。
