Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527, Athens, Greece.
Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527, Athens, Greece.
Cancer Lett. 2017 Apr 1;390:153-159. doi: 10.1016/j.canlet.2017.01.020. Epub 2017 Jan 19.
Glycative stress from endogenous and exogenous advanced glycation end-products (AGEs) has been implicated to cancer development and progression. Dicarbonyl compounds, the main AGE precursors and crosslinked AGE forms may directly react with proteins, lipids and nucleic acids, modify their structure and affect tissue microenvironment. They may also induce elevation of reactive oxygen species (ROS) and enhance cellular oxidative stress, an important regulator of cancer hallmarks. Moreover, the activation of AGE-receptor for AGE (RAGE) signalling pathways mediates inflammation, oxidative stress, autophagy and apoptosis leading to genomic instability and cancer initiation. Here, we provide evidence on the impact of glycative stress in promoting human tumorigenesis and we discuss the potential application of anti-glycating agents, RAGE and glyoxalase-1 inhibitors in cancer prevention.
糖基化应激来源于内源性和外源性的晚期糖基化终产物(AGEs),被认为与癌症的发生和发展有关。二羰基化合物是 AGE 的主要前体和交联 AGE 形式,它们可能直接与蛋白质、脂质和核酸反应,改变其结构并影响组织微环境。它们还可能诱导活性氧(ROS)的升高,增强细胞氧化应激,这是癌症特征的一个重要调节剂。此外,AGE 受体(RAGE)信号通路的激活介导炎症、氧化应激、自噬和细胞凋亡,导致基因组不稳定性和癌症的发生。在这里,我们提供了糖基化应激促进人类肿瘤发生的证据,并讨论了抗糖化剂、RAGE 和甘油醛-1 抑制剂在癌症预防中的潜在应用。