DHA- and EPA-Enriched Phosphatidylcholine Suppress Human Lung Carcinoma 95D Cells Metastasis via Activating the Peroxisome Proliferator-Activated Receptor γ

Abstract

The antineoplastic effects of docosahexaenoic acid-containing phosphatidylcholine (DHA-PC) and eicosapentaenoic acid-containing phosphatidylcholine (EPA-PC) were explored, and their underlying mechanisms in the human lung carcinoma 95D cells (95D cells) were investigated. After treatment of 95D cells with DHA-PC or EPA-PC, cell biological behaviors such as growth, adhesion, migration, and invasion were studied. Immunofluorescence and western blotting were carried out to assess underlying molecular mechanisms. Results showed that 95D cells proliferation and adherence in the DHA-PC or EPA-PC group were drastically inhibited than the control group. DHA-PC and EPA-PC suppressed the migration and invasion of 95D cells by disrupting intracellular F-actin, which drives cell movement. The protein expression of PPARγ was induced versus the control group. Furthermore, critical factors related to invasion, including matrix metallopeptidase 9 (MMP9), heparanase (Hpa), and vascular endothelial growth factor (VEGF), were drastically downregulated through the PPARγ/NF-κB signaling pathway. C-X-C chemokine receptor type 4 (CXCR4) and cofilin were significantly suppressed via DHA-PC and EPA-PC through the PPARγ/phosphatase and tensin homolog (PTEN)/serine-threonine protein kinase (AKT) signaling pathway. DHA-PC and EPA-PC reversed the PPARγ antagonist GW9662-induced reduction of 95D cells in migration and invasion capacity, suggesting that PPARγ was directly involved in the anti-metastasis efficacy of DHA-PC and EPA-PC. In conclusion, DHA-PC and EPA-PC have great potential for cancer therapy, and the antineoplastic effects involve the activation of PPARγ. EPA-PC showed more pronounced antineoplastic effects than DHA-PC, possibly due to the more robust activation of PPARγ by EPA-PC.

Oral Supplementation of Phosphatidylcholine Attenuates the Onset of a Diet-Induced Metabolic Dysfunction–Associated Steatohepatitis in Female C57BL/6J Mice

“…In line with these findings, TNF-α protein concentration was significantly (control diet [C] vs FrFC and C+phosphatidylcholine vs FrFC), and by trend, higher in livers of FrFC-fed mice than in FrFC+phosphatidylcholine–fed mice (FrFC vs FrFC+phosphatidylcholine: P = .09) ( Figure 4 E ). Because results of studies suggest that phosphatidylcholine may regulate peroxisome proliferator-activated receptor γ (PPARγ) and that PPARγ may alter NFκB activation, 25 , 26 we next determined the mRNA expression of the 2 splice variants of PPARγ: Pparg1 and 2 . Expression of Pparg1 mRNA expression was similar between groups ( Figure 4 F ).…”

Lung cancer progression alters lung and gut microbiomes and lipid metabolism

“…Additionally, leukotriene B4 (LTB4) and prostaglandin E2, which exacerbate lung cancer [ [24] , [25] , [26] , [27] ], are upregulated in the lungs. However, isohumulone, which is a peroxisome proliferator-activated receptor gamma (PPARγ) activator [ 28 ], and resolvin (an ω-3 PUFA), one of the specialized pro-resolving mediators (SPMs), which both have anti-cancer effects, were upregulated in the small intestine and colon [ [17] , [18] , [29] , [30] , [31] ].

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Preparation of Novel Sea Cucumber Intestinal Peptides to Promote Tibial Fracture Healing in Mice by Inducing Differentiation of Hypertrophic Chondrocytes to the Osteoblast Lineage

“…Western Blot Analysis: The western blot analysis was performed according to the previous protocol. [41] In short, 300 mg cartilage callus was homogenized in liquid nitrogen, and the total protein was extracted in 1 mL lysate (including phosphatase inhibitor). The protein concentration was measured with a BCA kit according to the instructions.…”