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

Abstract

Scope Glycation products are ubiquitous in food at high concentrations in the Western diet. The well‐controlled glycation resulting in the production of early glycation products (EGPs) has been proposed as a strategy to improve the physicochemical properties of food proteins. However, the health effects of EGPs are unknown. It has been shown that the Western diet (glycation prone) is associated with a higher mortality in prostate cancer (PCa) patients than the prudent diet; therefore, the role of EGPs in prostate tumorigenesis is investigated. Methods and results C57BL/6 male mice are treated with the vehicle (water), non‐reacted samples, EGPs, and advanced glycation end‐products (AGEs) by gavage. EGPs (600 mg kg−1 body weight per day) promoted the growth of subcutaneously transplanted TRAMP‐C2 PCa cells the most among these groups. Significantly, increases in the circulation monocytes and tumor‐associated M2 macrophages are observed in EGP‐treated mice, and the M2/M1 ratio is also increased in the EGP group when compared to that of water and AGEs. In the human PCa cell and macrophage co‐cultures, EGPs increase the spheroid size, and importantly, macrophages are also polarized toward M2. Conclusions EGPs induce the proliferation of PCa cells either directly or by assisting PCa cells to polarize macrophages toward M2.

Glycated whey proteins protect NOD mice against type 1 diabetes by increasing anti-inflammatory responses and decreasing autoreactivity to self-antigens

“…Importantly, IL-10-deficient mice experienced severe T1D (Tian et al, 2001). In our previous studies, IL-10 was also identified as one of the most up-regulated cytokines/chemokines when EGPs was applied to human macrophages (PMA-differentiated-U937 cells), peritoneal macrophages from C57BL/6 females (Chen et al, 2018), and C57BL/6 males (Chen & Guo, 2019).…”

“…In the small intestine, dietary protein antigens could induce periphery regulatory T cells (pTregs), which expressed high level of IL-10 and suppressed effector T cells (Kim et al, 2016). The consistently increased circulating IL-10 levels in both C57BL/6 males (Chen & Guo, 2019) and NOD females following EGP exposure suggested possible inductions of pTregs in the intestine, although other cells, such as M2 macrophages, CD4 + CD25 + Foxp3 − T cells ., regulatory B cells including CD19 hi CD1d hi CD5 + in mice (Yanaba et al, 2008) and CD24 hi CD27 + in humans (Iwata et al, 2011), could secrete IL-10 as well. In addition, the reduced intestinal absorption might increase the chances of gut fermentation.…”

“…Our previous studies showed that dietary EGPs could regulate the inflammatory processes when applied to human macrophages (phorbol 12-myristate 13-acetate (PMA)differentiated-U937 cells) (Chen, Filipov, & Guo, 2018), and polarize tumor-associated macrophages toward the anti-inflammatory phenotype M2 in C57BL/6 male mice (Chen & Guo, 2019), which implied an protective effect of EGPs against autoimmune dysregulation. Furthermore, the oral consumption of whey protein derived EGPs did not increase the serum CML level, excluding the possibility of biotransformation of EGPs into AGEs in physiological conditions (Chen & Guo, 2019). Therefore, it was hypothesized that EGPs could protect against T1D through the regulation of immune responses.…”

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“…Exogenous AGEs from food can be absorbed into the systemic circulation or cause inflammatory reactions at the colon level, as reviewed in [16]. The early glycation products from food were shown to promote prostate tumor growth more than AGEs [7]. Regardless of source (Maillard reaction or exogenous), AGEs may cause a direct destruction of the extracellular matrix or can trigger a receptormediated signaling cascade that results in the production of free radicals and proinflammatory molecules [28].…”