Conjugated Eicosapentaenoic Acid (EPA) Inhibits Transplanted Tumor Growth via Membrane Lipid Peroxidation in Nude Mice

• Published in: The Journal of nutrition Vol. 134; no. 5; pp. 1162 - 1166
• Main Authors: Tsuzuki, Tsuyoshi, Igarashi, Miki, Miyazawa, Teruo
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Elsevier Inc 01.05.2004; American Society for Nutritional Sciences; American Institute of Nutrition
• Subjects: Animals; Back; Biological and medical sciences; Cell Division - drug effects; Cell Line, Tumor; conjugated eicosapentaenoic acid; conjugated fatty acid; conjugated linoleic acid; DNA Fragmentation - drug effects; Eicosapentaenoic Acid - chemistry; Eicosapentaenoic Acid - pharmacology; Fatty acids; Fatty Acids - pharmacology; Feeding. Feeding behavior; Fundamental and applied biological sciences. Psychology; Humans; Linoleic Acids, Conjugated - pharmacology; lipid peroxidation; Lipid Peroxidation - drug effects; Lipids; Male; Membranes - metabolism; Mice; Mice, Nude; Neoplasm Transplantation; nude mice; Nutrition; Phospholipids - metabolism; Rodents; Skin Neoplasms - genetics; Skin Neoplasms - metabolism; Skin Neoplasms - pathology; Tumors; Vertebrates: anatomy and physiology, studies on body, several organs or systems; conjugated linoleic acid; PCOOH; PEOOH; FBS; EPA; nude mice; CLA; conjugated eicosapentaenoic acid; conjugated fatty acid; CEPA; lipid peroxidation; CL-HPLC; Conjugated linoleic acid; Nutrition; Rodentia; Polyunsaturated fatty acid; Lipids; Transplantation; Malignant tumor; n-3 fatty acid; Fatty acids; Vertebrata; Mammalia; Mouse; Animal; Unsaturated fatty acid; Membrane; Eicosapentaenoic acid; Peroxidation
• ISSN: 0022-3166; 1541-6100
• DOI: 10.1093/jn/134.5.1162

Both conjugated linoleic acid (CLA) and eicosapentaenoic acid (EPA) have an antitumor effect. Hence, we hypothesized that a combination of conjugated double bonds and an (n-3) highly unsaturated fatty acid would produce stronger bioactivity. To verify the antitumor effect of conjugated EPA (CEPA), we transplanted DLD-1 human colon tumor cells into nude mice, and compared the tumor growth between CEPA-fed mice and CLA- and EPA-fed mice. After tumor cell inoculation, mice were assigned to 1 of 4 groups (control, CLA, EPA, and CEPA) consisting of 10 mice each. The control group received only safflower oil fatty acids, whereas the remaining groups received a mixture of safflower oil fatty acids and 20 g/100 g of total fatty acids as CLA, EPA, or CEPA. Mice were fed once every 2 d for 4 wk at a dose of 50 mg/mouse at each feeding. After 4 wk, tumor growth in CEPA-fed mice was significantly suppressed, compared with that in CLA- (P < 0.005) and EPA-fed mice (P < 0.001). DNA fragmentation in the tumor tissues of the CEPA-fed mice occurred more frequently than in the CLA- (P < 0.001) and EPA-fed mice (P < 0.001), suggesting that CEPA induced apoptosis in the tumor tissues. To further investigate the mechanism, the level of oxidative stress in the tumor tissues was determined. The CEPA-fed mice showed significant lipid peroxidation, compared with the CLA- (P < 0.001) and EPA-fed mice (P < 0.001). Therefore, we verified that CEPA has a stronger in vivo antitumor effect than EPA and CLA, and that CEPA acts through induction of apoptosis via lipid peroxidation.