Suppressed liver tumorigenesis in fat-1 mice with elevated omega-3 fatty acids is associated with increased omega-3 derived lipid mediators and reduced TNF-α
| Autor: | Cheng-Ying Chiu, Anja Nadolny, Beate Gomolka, Lena F. Krause, Karsten H. Weylandt, Michael Rothe, Siileyman Bilal, Simon F. Waechter, Jing X. Kang, Andreas Fischer |
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| Rok vydání: | 2011 |
| Předmět: |
Fatty Acid Desaturases
Male Cancer Research medicine.medical_specialty Liver tumor Carcinoma Hepatocellular Chromatography Gas Docosahexaenoic Acids Blotting Western Inflammation Mice Transgenic Biology Proinflammatory cytokine Liver disease Mice Liver Neoplasms Experimental Internal medicine Fatty Acids Omega-3 medicine Animals RNA Messenger Caenorhabditis elegans Caenorhabditis elegans Proteins Unsaturated fatty acid Cells Cultured chemistry.chemical_classification Reverse Transcriptase Polymerase Chain Reaction Tumor Necrosis Factor-alpha Macrophages General Medicine medicine.disease digestive system diseases Endocrinology chemistry Docosahexaenoic acid Tumor necrosis factor alpha medicine.symptom Cancer Prevention Polyunsaturated fatty acid |
| Zdroj: | Carcinogenesis. 32(6) |
| ISSN: | 1460-2180 |
| Popis: | Liver tumors, particularly hepatocellular carcinoma (HCC), are a major cause of morbidity and mortality worldwide. The development of HCC is mostly associated with chronic inflammatory liver disease of various etiologies. Previous studies have shown that omega-3 (n-3) polyunsaturated fatty acids (PUFAs) dampen inflammation in the liver and decrease formation of tumor necrosis factor (TNF)-α. In this study, we used the fat-1 transgenic mouse model, which endogenously forms n-3 PUFA from n-6 PUFA to determine the effect of an increased n-3 PUFA tissue status on tumor formation in the diethylnitrosamine (DEN)-induced liver tumor model. Our results showed a decrease in tumor formation, in terms of size and number, in fat-1 mice compared with wild-type littermates. Plasma TNF-α levels and liver cyclooxygenase-2 expression were markedly lower in fat-1 mice. Furthermore, there was a decreased fibrotic activity in the livers of fat-1 mice. Lipidomics analyses of lipid mediators revealed significantly increased levels of the n-3 PUFA-derived 18-hydroxyeicosapentaenoic acid (18-HEPE) and 17-hydroxydocosahexaenoic acid (17-HDHA) in the livers of fat-1 animals treated with DEN. In vitro experiments showed that 18-HEPE and 17-HDHA could effectively suppress lipopolysacharide-triggered TNF-α formation in a murine macrophage cell line. The results of this study provide evidence that an increased tissue status of n-3 PUFA suppresses liver tumorigenesis, probably through inhibiting liver inflammation. The findings also point to a potential anticancer role for the n-3 PUFA-derived lipid mediators 18-HEPE and 17-HDHA, which can downregulate the important proinflammatory and proproliferative factor TNF-α. |
| Databáze: | OpenAIRE |
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