Dietary Glycation Products Regulate Immune Homeostasis: Early Glycation Products Promote Prostate Cancer Cell Proliferation through Modulating Macrophages

Scope: Well-controlled glycation (generally limited to the early stages) has been proposed as a strategy to improve the physiochemical properties of dietary proteins, but the functional studies of glycation products are mostly on advanced glycation end-products (AGEs) rather than early glycation products (EGPs). Since cytokines are important modulators of various biological processes, this study aims to determine whether EGPs and AGEs affected immune homeostasis differentially and do so through modulating macrophage-derived factors. Methods and results: Two systems (glycine-glucose and whey protein isolate (WPI)-glucose) are established to generate glycation products. They are applied to human macrophages (PMA-differentiated U937 cells), and cell viability and cytokine production are measured. Furthermore, EGPs, AGEs, and their conditioned medium (CM) from macrophages are applied to human prostate cancer (PCa) cells with different etiology (LNCaP and PC-3) and murine PCa cells (TRAMP-C2) to determine their direct and indirect effects on PCa cell proliferation. EGPs enhance the production of immunosuppressive cytokines, and this enhancement is associated with increased PCa cell proliferation. In contrast, AGEs inhibit macrophages to secret cytokines, but increase PCa cell proliferation directly. Conclusions: Our data suggest that EGPs promote the prostate tumor proliferation indirectly through modulating macrophages, while AGEs have a direct effect.