Effects of dietary fish oil on human mammary carcinoma and on lipid-metabolizing enzymes.
The growth rate of a human mammary carcinoma, MX-1, was significantly reduced in athymic "nude" mice fed fish oil. Tumors from the fish oil-fed animals also showed a greater sensitivity to two anti-neoplastic agents, mitomycin C and doxorubicin. Mitochondria were isolated from control livers, host livers and tumors from fish oil- and corn oil-fed animals, and increased levels of 20:5n-3 and 22:6n-3 were found in mitochondrial lipids in all three tissues from the fish oil-fed animals. To investigate the effect of dietary n-3 fatty acids on lipid metabolism, the activity of the acyl-CoA:carnitine acyltransferase and three acyl-CoA desaturases were measured. Carnitine acyltransferase activity toward all four acyl-CoA substrates tested was markedly increased in mitochondria from liver by feeding fish oil. In mitochondria from tumors, feeding fish oil resulted in an increased activity toward only 18:3n-3. These data suggest that fish oil may induce an increase in the oxidation of fatty acids. The delta 9-desaturase activity was decreased in microsomes from liver and tumor from fish oil-fed animals. However, both the delta 6 and delta 5 desaturases were increased in tumor and in control liver as a result of feeding fish oil. The delta 5 desaturase was not altered in microsomes from the host animals. The effect of fish oil on the delta 5 and delta 6 desaturases may involve alterations to metabolism of specific polyunsaturated fatty acids especially in the tumor tissue.
Borgeson
C E
CE
Department of Biochemistry, University of Nevada, Reno 89557.
Pardini
L
L
Pardini
R S
RS
Reitz
R C
RC
D000217:Acyltransferases / Q000378:metabolism*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002333:Carnitine Acyltransferases / Q000378:metabolism*; D004042:Dietary Fats, Unsaturated / Q000494:pharmacology*; D004317:Doxorubicin / Q000494:pharmacology; D044943:Fatty Acid Desaturases / Q000378:metabolism; D005260:Female; D005395:Fish Oils / Q000494:pharmacology*; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000201:enzymology* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D008930:Mitochondria, Liver / Q000378:metabolism; D016685:Mitomycin; D008937:Mitomycins / Q000494:pharmacology; D009368:Neoplasm Transplantation
D004042:Dietary Fats, Unsaturated; D005395:Fish Oils; D008937:Mitomycins; D016685:Mitomycin; D004317:Doxorubicin; D044943:Fatty Acid Desaturases; D000217:Acyltransferases; D002333:Carnitine Acyltransferases