Advanced glycation end-products (AGEs) are proteins or lipids glycated nonenzymatically by glucose, or other reducing sugars and their derivatives, such as glyceraldehyde, glycolaldehyde, methyloglyoxal and acetaldehyde. There are three different means of AGE formation: i) Maillard reactions, the polyol pathway and lipid peroxidation. AGEs participate in the pathological mechanisms underlying the development of several diseases, such as diabetes and its complications, retinopathy or neuropathy, neurological disorders (for example, Parkinson's disease and Alzheimer's disease), atherosclerosis, hypertension and several types of cancer. AGE levels are increased in patients with hyperglycaemia, and is likely the result of the high concentration of glycation substrates circulating in the blood. The present review summarises the formation and nomenclature of advanced glycation end-products, with an emphasis on the role of AGEs in the development of diabetes, neurological disorders, as well as in cancer and other pathologies. A particular focus is placed on the functions of toxic AGEs. Additionally, studies which have shown the cytotoxicity of glycated albumin and other AGEs are also discussed. Finally, the diagnostic relevance of AGEs as well as for targeting in therapeutic strategies are highlighted.

Cancer is a complex disease with a 5-10% hereditary base, but nutrition, lifestyle, and the environment we are exposed to influence 90-95% of cancers. Due to rapid westernization, the diet we consume is rich in advanced glycation end products (AGEs). AGEs are the heterogeneous group of compounds formed by non-enzymatic reactions between reducing sugars and amino groups of proteins, lipids, and nucleic acids. Its implication is confirmed in many chronic conditions such as diabetes, renal, cardiovascular diseases, and aging however its role in cancer development has been understudied. Cancer cells are continuously exposed to AGEs due to their increased production, owing to its high metabolic rate and aerobic glycolysis. AGEs accumulation led to glycative stress which in turn stimulates oxidative stress and inflammation, through its receptor known as receptor for advanced glycation end products (RAGE). RAGE mediates crosstalk between the tumour cells and its microenvironment components to induce hypoxia, mitochondrial dysfunction, endoplasmic reticulum stress, autophagy, epigenetic modification, and cancer stemness. This emphasizes AGEs as an essential driving factor in different aspects of cancer development, but the exact molecular mechanism has to be explored. Thus, this review gives an insight into the pathological role of AGEs at the bio-molecular level in the tumourigenesis and progression of cancer in terms of the tumour microenvironment, invasion, and metastasis. Further, the compiled clinical data relating to the AGE-RAGE axis associated with different cancers and its potential inhibitors have been discussed.

Advanced Glycation End products (AGEs) are basically the end result of glycation of proteins and/or lipids in the presence of sugars. Specific cases of hyperglycemia have been reported with increased propensity of generation of AGEs. Many chronic and deadly diseases such as diabetes, cancer and neurodegenerative disorders have been known to be caused as a result of generation of AGEs. The role of glutathione (GSH) metabolism and its intricate association with AGEs have also been well established in breast cancer prognosis and treatment. To understand the etiology, mechanism and production of AGEs along with clinical relevance of Receptors for Advanced Glycation End-products (RAGE) and RAGE ligands, their interplay with GSH is of paramount importance especially in relation to breast cancer. The available literature using PubMed, National Library of Medicine database, Web of Science and SCOPUS indexed, Science Direct and other prestigious journals have been systematically reviewed using the keywords: advanced glycation end-products, breast cancer, glutathione RAGE, and AGEs inhibitors. This narrative review of all the relevant papers with significant citations has led us to have greater insight into the action mechanism and potential therapeutic significance of AGEs inhibitors. Targeting breast cancer with the specific immunoglobulins and with other therapeutic interventions is needed to inhibit the generation of AGEs and manage glutathione expression, thus having strong implications in the management of breast cancer. Many RAGE ligands such as HMGB1, S100P, S100A8, S100A9 etc. have been known to enhance RAGE expression which may further lead to increased proliferation, migration and metastatic nature of tumor cells. Hence, RAGE and RAGE ligands in a close linkup with GSH may prove to be effective therapeutic markers of severity of breast cancer and for angiogenesis of tumor. This review provides a strong platform to comprehend the etiology, mechanism and production of AGEs and glutathione along with the agents which can block their production, paving a way for the therapeutic intervention and an amicable solution to treat and manage breast cancer.

Objective: Glycation is the chemical reaction involving the modification of proteins and amino acids in the presence of reducing sugars, and advanced glycation end products (AGEs) are heterogeneous compounds whose accumulation is implicated as the pathogenesis in various chronic diseases.Method: A narrative review of all the articles known to the authors was conducted.Results: Tobacco and diet are the two major sources of exogenous AGE and the foremost characteristic of the glycotoxins, formed from tobacco curing reaction, is their high reactivity and innate ability to cross the cell membrane and bind with serum proteins and formation of adducts with amino acids of nucleic acids. Binding of AGEs to their receptor for AGE activates mechanisms which favor production of reactive oxidative species and proinflammatory cytokines. AGEs are also implicated as key players in cell survival, proliferation, invasion, and metastasis of tumor cells and also significantly contribute to genotoxicity. Salivary estimation of AGEs is a promising exposition to monitor the prognosis of oral pre-cancers and cancer.Conclusion: This review aims in eliciting the role of AGEs in pathogenesis of oral cancer and its possible development as a biomarker to monitor the initiation and progression of cancer.

Advanced glycation end products (AGEs) are nonenzymatic modifications of proteins by reducing sugars. These compounds accumulate in a number of chronic disease states, contributing to tissue injury via several mechanisms, including activation of the receptor for advanced glycation end products (RAGE). We aimed to investigate whether AGEs can exacerbate chronic liver injury and contribute to hepatic fibrosis. We initially studied the effects of chronic hepatic exposure to high levels of AGEs given intraperitoneally as AGE-rat serum albumin. In a separate experiment, we examined the impact of high AGE exposure in rats following bile duct ligation (BDL). In normal rats, chronic AGE-rat serum albumin administration induced significant increases in α-smooth muscle actin gene and protein expression but did not induce fibrosis or biochemical evidence of liver injury. However, in BDL animals, AGE-bovine serum albumin administration significantly increased hepatic fibrosis as evidenced by increased collagen content and α-smooth muscle actin expression, compared with BDL alone. Furthermore, AGEs increased hepatic oxidative stress and receptor for advanced glycation end products gene expression. These findings suggest that AGEs may contribute to the pathogenesis of chronic liver injury and fibrosis.

Advanced glycation end products (AGEs) are reactive metabolites under physiological and pathological conditions. They accumulate in tissues and organs and are involved in the pathogenesis of various diseases including cancer. This review presents recent findings on the roles of AGEs and their receptor (RAGE) in carcinogenesis. The molecular mechanisms of cancer pathogenesis and progression related to AGEs-RAGE interaction are highlighted. The strategies for AGE reduction and inhibition in the potential prevention and treatment of cancers are discussed.

Diabetic patients have increased levels of advanced glycation end products (AGEs) and the role of AGEs in regulating cancer cell proliferation is unclear. Here, we found that treating colorectal and liver cancer cells with AGEs promoted cell proliferation. AGEs stimulated both the expression and activation of a key transcription factor called carbohydrate responsive element binding protein (ChREBP) which had been shown to promote glycolytic and anabolic activity as well as proliferation of colorectal and liver cancer cells. Using siRNAs or the antagonistic antibody for the receptor for advanced glycation end-products (RAGE) blocked AGEs-induced ChREBP expression or cell proliferation in cancer cells. Suppressing ChREBP expression severely impaired AGEs-induced cancer cell proliferation. Taken together, these results demonstrate that AGEs–RAGE signaling enhances cancer cell proliferation in which AGEs-mediated ChREBP induction plays an important role. These findings may provide new explanation for increased cancer progression in diabetic patients.

Advanced glycation end products lead to cell apoptosis, and cause cell death by increasing endoplasmic reticulum stress. Advanced glycation end products alone may also directly cause damage to tissues and cells, but the precise mechanism remains unknown. This study used primary cultures of rat cerebral cortex neurons, and treated cells with different concentrations of glycation end products (50, 100, 200, 400 mg/L), and with an antibody for the receptor of advanced glycation end products before and after treatment with advanced glycation end products. The results showed that with increasing concentrations of glycation end products, free radical content increased in neurons, and the number of apoptotic cells increased in a dose-dependent manner. Before and after treatment of advanced glycation end products, the addition of the antibody against advanced glycation end-products markedly reduced hydroxyl free radicals, malondialdehyde levels, and inhibited cell apoptosis. This result indicated that the antibody for receptor of advanced glycation end-products in neurons from the rat cerebral cortex can reduce glycation end product-induced oxidative stress damage by suppressing glycation end product receptors. Overall, our study confirms that the advanced glycation end products-advanced glycation end products receptor pathway may be the main signaling pathway leading to neuronal damage.

Advanced glycation end products(AGEs)are important factors leading to cardiovascular complications of diabetes mellitus. After further study and discussion, we found that pathophysiology of AGEs on vascular smooth muscle cells(VSMC)was one of the key procedures. In this process, AGEs bind to its receptor(RAGE)on the surface of the VSMC, leading to a series of proinflammatory and thrombotic responses. AGEs induce VSMC proliferation, migration, calcification and interfere their contractile phenotype and function. Knowing the mechanism and finding antagonistic inhibitors will help guide our clinical prevention and treatment. In this paper, AGEs and RAGE on VSMC mechanism were reviewed. Key words: Advanced glycation end products; Receptor for advanced glycation end products; Vascular smooth muscle cell; Diabetic vascular complications

Advanced glycation end products(AGEs)are important biochemical abnormality associated with the development of diabetes mellitus.Here we summarize recent relative basic and clinical studies about mechanism of AGEs on the formation and progression of atherosclerosis in cellular and molecular level, including effect on extracellular, modification of low density lipoprotein, vascular dysfunction, oxidative stress and immune-inflammatory responses.We especially focus on interaction of AGEs with its receptor, activating the downstream signaling pathway, promoting expression of relative gene and the generation of reactive oxygen species, and accelerating progression of atherosclerosis.A better understanding of AGEs for formation atherosclerosis will help us to develop strategies for the prevention and treatment of diabetic atherosclerosis. Key words: Glycosylation end products, advanced; Atherosclerosis; Oxidative stress; Inflammatory response