The effects of dietary polyunsaturated fatty acids on prostate cancer: Unbiased proteomic and phosphoproteomic studies

Abstract

A line of evidence has suggested that early inference and dietary prevention are beneficial in prostate cancer (PCa) patient care. Fish oil (FO), which contains mostly omega-3 polyunsaturated fatty acid, is one of the most widely studied candidate supplements for PCa prevention; however, the molecular mechanism remains elusive. The goal of this study is to evaluate the regulatory role of FO on PCa through a global unbiased proteomic analysis and a global phosphoproteomic profiling. In the global protein expression study, we found only a few proteins with statistically significant changes, including sequestosome-1 (p62), MSMP, a newly identified proinflammation factor, and a few in the glycolysis pathway. In the global phosphoproteomic study, we confidently identified 828 phosphopeptides from 361 phosphoproteins with FDR < 1%. Quantitative comparison between treatment and control groups suggests that FO induces changes in protein phosphorylation of proteins involved in pathways associated with cell viability and metabolic processes, specifically significant decreases in the levels of phospho-PDHA1Ser232 and phospho-PDHA1Ser300, suggesting a role for n-3 polyunsaturated fatty acids in controlling the balance between lipid and glucose oxidation. This study confirmed that FO changed PCa cell function through diverse pathways including glycolysis, cell cycle, cytotoxicity induced stress, anti-inflammation and also provided useful details about the mechanism of these effects. A global proteome and phosphoproteome clinical study in PCa clinical samples would validate and extend these findings to the patient population and potentially provide novel opportunities for therapeutic development.