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.