Abstract
EPA-enriched phosphatidylcholine (EPA-PC) and EPA-enriched phosphatidylethanolamine (EPA-PE) are newly identified marine phospholipids. The polar group of phospholipids is known to influence EPA-phospholipid activity. However, the differences in anti-tumor effects between EPA-PC and EPA-PE have not been reported. In this study, we evaluated the effects of two forms of EPA on the proliferation and apoptosis in the lung-cancer cell line 95D as well as possible molecular mechanisms. Our results showed that EPA-PC effectively inhibited proliferative activity and promoted apoptosis of 95D cells in a dose-dependent manner, while EPA-PE had no effect on cell proliferation, although it slightly promoted apoptosis. Western blot results showed that EPA-PC and EPA-PE upregulated the expression of PPARγ, RXRα, and PTEN, and downregulated the PI3K/AKT signaling pathway. Furthermore, EPA-PC and EPA-PE induced the expression of the pro-apoptotic gene, Bax, and reduced the expression of the anti-apoptotic gene, Bcl-xl. Additionally, EPA-PC and EPA-PE promoted the release of cytochrome c and activated the apoptotic enzyme-cleaved caspase-3. These data suggest that the anti-tumor effect of EPA-phospholipids may be exerted via a PPARγ-related mechanism. EPA-PC was more efficacious as compared to EPA-PE, which might be due to the different polar groups of phospholipids.