Murray-Stewart Tracy R, Woster Patrick M, Casero Robert A
The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, 1650 Orleans Street, Bunting, Blaustein Building, Room 551, Baltimore, MD 21287, USA.
Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, SC 29425, USA.
Biochem J. 2016 Oct 1;473(19):2937-53. doi: 10.1042/BCJ20160383.
The chemically simple, biologically complex eukaryotic polyamines, spermidine and spermine, are positively charged alkylamines involved in many crucial cellular processes. Along with their diamine precursor putrescine, their normally high intracellular concentrations require fine attenuation by multiple regulatory mechanisms to keep these essential molecules within strict physiologic ranges. Since the metabolism of and requirement for polyamines are frequently dysregulated in neoplastic disease, the metabolic pathway and functions of polyamines provide rational drug targets; however, these targets have been difficult to exploit for chemotherapy. It is the goal of this article to review the latest findings in the field that demonstrate the potential utility of targeting the metabolism and function of polyamines as strategies for both chemotherapy and, possibly more importantly, chemoprevention.
化学结构简单但生物学功能复杂的真核多胺，亚精胺和精胺，是带正电荷的烷基胺，参与许多关键的细胞过程。与它们的二胺前体腐胺一起，其通常较高的细胞内浓度需要通过多种调节机制进行精细调控，以将这些必需分子维持在严格的生理范围内。由于多胺的代谢和需求在肿瘤疾病中经常失调，多胺的代谢途径和功能提供了合理的药物靶点；然而，这些靶点一直难以用于化疗。本文的目的是综述该领域的最新发现，这些发现表明将多胺的代谢和功能作为化疗策略，以及可能更重要的是作为化学预防策略具有潜在的实用性。
