Prognostic Potential and Tumor Growth-Inhibiting Effect of Plasma Advanced Glycation End Products in Non-Small Cell Lung Carcinoma

Abstract

The plasma fluorescence related to the standard fluorescence of advanced glycation end products (AGEs) is a simple measurable blood parameter for distinct diseases but its importance in human cancer, including non-small cell lung carcinoma (NSCLC), is unknown. Plasma samples of 70 NSCLC patients who underwent resection surgery of the tumor were analyzed for the distinct AGE-related fluorescence at 370 nm excitation/440 nm emission. In a retrospective study, we tested the prognostic relevance of this AGE-related plasma fluorescence. The effect of circulating AGEs on the NSCLC growth was studied experimentally in vitro and in vivo. NSCLC patients with high (> median) AGE-related plasma fluorescence were characterized by a later reoccurrence of the tumor after curative surgery and a higher survival rate compared with patients with low plasma fluorescence (25% versus 47% 5-y survival, P = 0.011). Treating NSCLC cell spheroids with patients' plasma showed an inverse correlation between the growth of spheroids in vitro and the individual AGE-related fluorescence of each plasma sample. To confirm the impact of circulating AGEs on the NSCLC progression, we studied the NSCLC growth in mice whose circulating AGE level was elevated by AGE-rich diet. In vivo tumorigenicity assays demonstrated that mice with higher levels of circulating AGEs developed smaller tumors than mice with normal AGE levels. The AGE-related plasma fluorescence has prognostic relevance for NSCLC patients in whom the tumor growth-inhibiting effect of circulating AGEs might play a critical role.

Protein glycation — Between tissue aging and protection

“…Moreover, it was shown that AGEs from nutrition also have beneficial effects. For an example, nude mice fed with AGEs from bread crust and increased levels of AGEs in the blood showed a reduced growth of lung cancer in comparison to mice with normal AGE levels (Bartling et al, 2011a). This is in line with data mentioned above that lung cancer patients with high AGErelated fluorescence in plasma have a better postoperative long-term survival.…”

“…Nonsmall cell lung carcinoma patients with high AGE-related plasma fluorescence have a later reoccurrence of the tumor after curative surgery and a higher survival rate compared with patients with low AGErelated plasma fluorescence. In an animal mouse model of the same study, an AGE rich diet was able to reduce the development of tumors (Bartling et al, 2011a). In line with these results, it could be shown that lung cancer patients with diabetes may have some advantages in the survival after tumor resection within the first one-to two years (Bartling et al, 2011b).…”

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

“…Notably, glyceraldehyde-derived AGE has been shown to significantly inhibit proliferation of A549 lung cancer cells, but it enhances the migrated and invasive activities of these cells [60]. In terms of lung tumor growth, these findings are partially in accordance with the clinical outcomes [49].…”

“…Systematic reviews indicate that a high-AGE diet that often recognized as a Western-style diet containing high-fat/high-sugar foods, refined grains, and red meat [25] or an unhealthy/sedentary lifestyle may increase the body's AGE pool, thereby increasing the risk of cancers such as prostate and pancreatic cancer [25][26][27][42][43][44]. In addition, a series of epidemiological studies have elucidated the association of biological AGE levels with the risk of cancer in smokers [45][46][47][48] and cancer patients [49][50][51]. Studies in Finnish male smokers found that serum CML levels were not associated with the risk of pancreatic or colorectal cancer and were inversely associated with the risk of liver cancer [45][46][47].…”

Non-enzymatic glycation of α-crystallin as an in vitro model for aging, diabetes and degenerative diseases

“…Dicarbonyl intermediates such as methyl glyoxal cause a lot of structural damage compared to reducing sugars such as glucose. The rate of AGE formation depends on the rate of the formation of highly reactive intermediates due to defective glycolysis pathway and consumption of high sugar diet (Bartling et al 2011;Simm et al 2014). The change in AGE fluorescence with decrease in tryptophan fluorescence can be observed in Fig.…”