Effect of cis-unsaturated fatty acids on Meth-A ascitic tumour cells in vitro and in vivo.
Earlier studies performed both by us and by others have demonstrated that some n-3 and n-6 fatty acids can inhibit the growth of tumour cells in vitro. Though studies done with various types of oils rich in n-3 and n-6 fatty acids did show that the tumour incidence and growth can be modified, there were relatively few studies wherein the anti-tumour effects of individual free fatty acids were studied. Here we present results which suggest that free fatty acids (oleic acid (OA), linoleic acid (LA), alpha-linolenic acid (ALA), gamma-linolenic acid (GLA), arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) can inhibit the growth of methylcholanthrene-induced sarcoma cells (Meth-A cells) in vitro. The order of potency of various fatty acids on the growth of Meth-A cells was DHA > ALA > EPA > AA > GLA > LA > OA and their ID50 values were 10, 20, 35, 45, 68, 73 and 110 microg/ml/1 x 10(4) cells, respectively. These results indicate that the inhibitory action of different types of n-3, n-6 and n-9 fatty acids on Meth-A cells does not depend on their unsaturation. Vitamin E could partially block the cytotoxicity of these fatty acids indicating a possible role for free radicals. GLA, AA and EPA augmented the generation of superoxide anion and lipid peroxidation in Meth-A cells indicating a possible correlation between the ability of fatty acids to augment free radicals and their tumoricidal action. In an in vivo study, it was observed that OA, LA, ALA, GLA and EPA can prolong the survival of Meth-A-bearing mice when given intraperitoneally. Of all the fatty acids tested, surprisingly, LA was found to be the most potent in enhancing the survival of the tumour-bearing animals at all the concentrations tested. Thus, these studies suggest that free fatty acids can inhibit Meth-A tumour cell proliferation both in vitro and in vivo.
Ramesh
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G
Division of Internal Medicine, Clinical Immunology and Biochemistry, L.V. Prasad Eye Institute, Hyderabad, India.
Das
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D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004281:Docosahexaenoic Acids / Q000494:pharmacology; D015118:Eicosapentaenoic Acid / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D019787:Linoleic Acid / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects; D008748:Methylcholanthrene; D051379:Mice; D008807:Mice, Inbred BALB C; D019301:Oleic Acid / Q000494:pharmacology; D012513:Sarcoma, Experimental / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors; D014810:Vitamin E / Q000494:pharmacology; D017962:alpha-Linolenic Acid / Q000494:pharmacology; D017965:gamma-Linolenic Acid / Q000494:pharmacology
D005231:Fatty Acids, Unsaturated; D017962:alpha-Linolenic Acid; D013481:Superoxides; D014810:Vitamin E; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D019301:Oleic Acid; D008748:Methylcholanthrene; D017965:gamma-Linolenic Acid; D019787:Linoleic Acid; D015118:Eicosapentaenoic Acid