Glycative stress from advanced glycation end products (AGEs) and dicarbonyls: An emerging biological factor in cancer onset and progression

• Published in: Molecular nutrition & food research Vol. 60; no. 8; pp. 1850 - 1864
• Main Authors: Lin, Jer-An, Wu, Chi-Hao, Lu, Chi-Cheng, Hsia, Shih-Min, Yen, Gow-Chin
• Format: Journal Article
• Language: English
• Published: Germany Blackwell Publishing Ltd 01.08.2016
• Subjects: advanced glycation end products; AGEs; Biological Factors; Cancer; carcinogenesis; Dicarbonyls; DNA; Glycation End Products, Advanced - metabolism; glycolysis; Glycosylation; lipid peroxidation; lipids; neoplasms; Neoplasms - prevention & control; Oxidation-Reduction; protein degradation; Pyruvaldehyde - metabolism; RAGE; reactive oxygen species; Reactive Oxygen Species - metabolism; Receptor for Advanced Glycation End Products - metabolism; reducing sugars; ROS; therapeutics; AGEs; RAGE; Dicarbonyls; ROS; Cancer
• ISSN: 1613-4125; 1613-4133; 1613-4133
• DOI: 10.1002/mnfr.201500759

In recent years, glycative stress from exogenous or endogenous advanced glycation end products (AGEs) and highly reactive dicarbonyls has gained great attention for its putative effects on cancer development. AGEs are a group of compounds formed from the complex chemical reaction of reducing sugars with compounds containing an amino group. AGEs bind to and activate the receptor for AGEs (RAGE), which is a predominant modulator of inflammation‐associated cancer, and AGEs induce reactive oxygen species that are an important regulator of the hallmarks of cancer. Dicarbonyls, which are formed during glycolysis, lipid oxidation, or protein degradation, include glyoxal, methylglyoxal, and 3‐deoxyglucosone and are regarded as major precursors of AGEs. These dicarbonyls not only fuel the AGE pool in living organisms but also evoke carbonyl stress, which may contribute to the carbonylative damage of carbohydrates, lipids, proteins, or DNA. Carbonylative damage then leads to many lesions, some of which are implicated in the pathogenesis of cancer. In this review, studies regarding the effects of AGEs and dicarbonyls on cancer onset or progression are systematically discussed, and the utilization of AGE inhibitors and dicarbonyl scavengers in cancer therapy are noted. The scheme of AGEs, dicarbonyls, ROS, and inflammation in cancer onset and progression. Exogenous and endogenous AGEs/dicarbonyls induce bursts of ROS and create a chronic inflammatory state. In such conditions, AGEs, dicarbonyls, ROS and pro‐inflammatory mediators interact in a positive feedback loop, leading to cancer onset or the enhancement of cancer progression.