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

Abstract

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.

Dietary Early Glycation Products Promote the Growth of Prostate Tumors More than Advanced Glycation End‐Products through Modulation of Macrophage Polarization

“…Oral administration of additional AGEs increased the CML level in sera, and this amount of AGEs did not generate overt toxicity to healthy mice but promoted the PCa development. Glycative stress from AGEs was concluded as a factor for cancer onset and progression, including PCa, and activation of the receptor for AGEs (RAGE)/sRAGE was considered the major molecular mechanism . Previous studies identified an increased expression of RAGE on both PCa cells and pro‐tumoral TAMs (in glioma) .…”

Evolving Evidence of Methylglyoxal and Dicarbonyl Stress Related Diseases from Diabetic to Non-Diabetic Models

“…The binding of MGO and GLO1 is the reaction rate-determining step. Most studies of MGO in diabetes and cancer focus on GLO1 function [1,21]. The effect of MGO on GLO1 is two-pronged.…”

Advanced glycation end products stimulate gene expression of fibroblast growth factor 23

“…Advanced glycation end products (AGEs) are generated by the non‐enzymatic reaction of sugars with proteins or lipids . They are produced in the body and in the process of preparing food .…”

“…Advanced glycation end products (AGEs) are generated by the non‐enzymatic reaction of sugars with proteins or lipids . They are produced in the body and in the process of preparing food . Aging, degenerative disorders, and in particular metabolic diseases including diabetes are associated with enhanced formation of AGEs .…”

“…They are produced in the body and in the process of preparing food . Aging, degenerative disorders, and in particular metabolic diseases including diabetes are associated with enhanced formation of AGEs . AGEs are known to activate NFκB .…”