title: Effects of eicosapentaenoic acid and docosahexaenoic acid on prostate cancer cell migration and invasion induced by tumor-associated macrophages.
abstract: Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are the major n-3 polyunsaturated fatty acids (PUFAs) in fish oil that decrease the risk of prostate cancer. Tumor-associated macrophages (TAMs) are the main leukocytes of intratumoral infiltration, and increased TAMs correlates with poor prostate cancer prognosis. However, the mechanism of n-3 PUFAs on prostate cancer cell progression induced by TAMs is not well understood. In this study, we investigated the effects of EPA and DHA on modulating of migration and invasion of prostate cancer cells induced by TAMs-like M2-type macrophages. PC-3 prostate cancer cells were pretreated with EPA, DHA, or the peroxisome proliferator-activated receptor (PPAR)-γ antagonist, GW9662, before exposure to conditioned medium (CM). CM was derived from M2-polarized THP-1 macrophages. The migratory and invasive abilities of PC-3 cells were evaluated using a coculture system of M2-type macrophages and PC-3 cells. EPA/DHA administration decreased migration and invasion of PC-3 cells. The PPAR-γ DNA-binding activity and cytosolic inhibitory factor κBα (IκBα) protein expression increased while the nuclear factor (NF)-κB p65 transcriptional activity and nuclear NF-κB p65 protein level decreased in PC-3 cells incubated with CM in the presence of EPA/DHA. Further, EPA/DHA downregulated mRNA expressions of matrix metalloproteinase-9, cyclooxygenase-2, vascular endothelial growth factor, and macrophage colony-stimulating factor. Pretreatment with GW9662 abolished the favorable effects of EPA/DHA on PC-3 cells. These results indicate that EPA/DHA administration reduced migration, invasion and macrophage chemotaxis of PC-3 cells induced by TAM-like M2-type macrophages, which may partly be explained by activation of PPAR-γ and decreased NF-κB p65 transcriptional activity.
authors.affiliation: School of Nutrition and Health Sciences, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan.
authors.forename: Cheng-Chung
authors.initials: CC
authors.lastname: Li
authors.affiliation: Department of Surgery, National Taiwan University, Taipei, Taiwan.
authors.forename: Yu-Chen
authors.initials: YC
authors.lastname: Hou
authors.affiliation: Department of Nutrition and Health Sciences, Chinese Culture University, Taipei, Taiwan.
authors.forename: Chiu-Li
authors.initials: CL
authors.lastname: Yeh
authors.affiliation: School of Nutrition and Health Sciences, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan.
authors.forename: Sung-Ling
authors.initials: SL
authors.lastname: Yeh
mesh_terms: D002465:Cell Movement / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D006801:Humans; D008262:Macrophage Activation / Q000187:drug effects / Q000502:physiology; D008264:Macrophages / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D008297:Male; D009361:Neoplasm Invasiveness; D011471:Prostatic Neoplasms / Q000473:pathology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D017077:Culture Media, Conditioned; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid; D013755:Tetradecanoylphorbol Acetate