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

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.