Cytotoxic action of alpha-linolenic and eicosapentaenoic acids on myeloma cells in vitro.
Both alpha-linolenic (ALA) and eicosapentaenoic acids (EPA) were toxic to SP 2/0 mouse myeloma cells in vitro. On the other hand, linoleic acid (LA), gamma-linolenic acid (GLA), di-homo-gamma linolenic acid (DGLA), arachidonic acid (AA), docosahexaenoic acid (DHA) and oleic acid (OA) were much less effective in their growth suppressive actions. Both nordihydroguaiaretic acid (NDGA) and Indomethacin (IM) could block the action of the fatty acids indicating a role for prostaglandins (PGs) and leukotrienes (LTs) in the growth suppressive action of ALA and EPA. Superoxide dismutase (SOD) completely blocked, while vitamin E and reduced glutathione (GSH) could prevent to a limited extent the anti-proliferative effects of ALA and EPA. Catalase, mannitol, chlorpromazine (CPZ) and trifluoperazine (TFP) did not block the cytotoxic actions of ALA and EPA. N(G)-mono-methyl L-arginine (N(G)MMA), an analogue of L-arginine, which inhibits nitric oxide synthase, was ineffective in preventing the cytotoxicity induced by ALA and EPA. Fatty acid analysis of the various lipid fractions of SP 2/0 cells treated with ALA and EPA showed significant incorporation of these fatty acids in the cell membrane lipid pools. These results suggest that ALA and EPA induced suppression of SP 2/0 cell proliferation is cyclo-oxygenase (CO), lipoxygenase (LO) and superoxide dependent. Lipid peroxidation has only a limited role in this process. Both calmodulin dependent process and L-arginine derived nitric oxide do not seem to have a role in the cytotoxic action of ALA and EPA in these cells.
Sravan Kumar
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Department of Medicine, L.V. Prasad Eye Institute, Hyderabad, India.
Das
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D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D001120:Arginine / Q000378:metabolism; D002147:Calmodulin / Q000037:antagonists & inhibitors; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated / Q000032:analysis / Q000494:pharmacology; D005978:Glutathione / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D051379:Mice; D009101:Multiple Myeloma / Q000378:metabolism / Q000473:pathology*; D011453:Prostaglandins / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014810:Vitamin E / Q000494:pharmacology; D017962:alpha-Linolenic Acid / Q000494:pharmacology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D002147:Calmodulin; D016861:Cyclooxygenase Inhibitors; D005231:Fatty Acids, Unsaturated; D016859:Lipoxygenase Inhibitors; D011453:Prostaglandins; D017962:alpha-Linolenic Acid; D014810:Vitamin E; D019323:omega-N-Methylarginine; D001120:Arginine; D015118:Eicosapentaenoic Acid; D005978:Glutathione; D007213:Indomethacin