Dietary Early Glycation Products Promote Prostate Tumorigenesis through Modulating Macrophages

Abstract

Abstract Glycation products are ubiquitous in food. Moreover, the well-controlled glycation, that results in the production of early glycation products (EGPs), has been proposed as a strategy to improve the physicochemical properties of the food proteins. However, the health effects of EGPs are rarely known. Since there is evidence showing that Western diet (glycation prone) is associated with higher mortality of prostate patients than Prudent diet, we investigated the role of EGPs in prostate tumorigenesis. EGPs were produced from a whey protein isolate-glucose model system, with non-reacted samples (NR) and advanced glycation end-products (AGEs) as controls. They were used to gavage male C57BL6 mice, and the mice were then subcutaneously injected with TRAMP-C2 cells (a mouse prostate cancer (PCa) cell line) in the flank area. The tumor length, width, and the proliferation index were measured, and the splenic leukocytes were studied. In addition, the mouse TRAMP-C2 cells and two human PCa cell lines LNCaP and PC-3 were cultured with NR, EGPs and AGEs, and LNCaP and PC-3 were further cultured with the conditioned medium generated from human macrophages. The PCa cell proliferation, and the cytokine/chemokine production and iNOS expression by macrophages were determined. The results showed that EGPs promoted prostate tumor growth most in vivo, and PCa cell proliferation only when the presence of macrophages in vitro. In addition, EGPs activated the production of most cytokines/chemokines examined, with IL-10 and MIP-1β unregulated most, and decreased the iNOS expression in macrophage. In conclusion, EGPs promoted PCa possibly by modulating macrophages to become prostate tumor-associated M2, which produced high levels of IL-10 and MIP-1β.