Metabolic and molecular regulation of dietary polyunsaturated fatty acids on prostate cancer

Purpose: The aim of this study is to investigate the role of n-3 and n-9 fatty acids in crucial processes involved in prostate cancer cell growth through a large-scale proteomic analysis. Experimental design: We used a label-free protein quantification method to profile global protein expression of fish oil and oleic acid treated PCa cells and validated a panel of differentially expressed proteins by either Western blot or multiple reaction monitoring. Bioinformatic analysis was also performed to uncover the pathways involved in fatty acid metabolism. Results: Fish oil, not oleic acid, suppresses prostate cancer cell viability. Assessment of fatty acid synthesis pathway activity also shows that oleic acid is a more potent inhibitor than fish oil on de novo fatty acid synthesis. Although fatty acid synthase activity decreases with fish oil treatment, the inhibition of its activity occurs over time while reduction in viability occurs within 24 h. Bioinformatic analysis revealed the pathways altered by these fatty acid treatments. Conclusions and clinical relevance: This study suggests that suppression of cell viability by fish oil is independent of fatty acid synthase and fish oil regulates prostate cancer cells through activation of other pathways depending upon length of exposure to fish oil.