Effects of polyunsaturated fatty acids on the efficacy of antineoplastic agents toward L5178Y lymphoma cells.
Modification of cultured lymphoma cells (L5178Y) with individual unsaturated fatty acids [oleic acid (OA), linoleic acid (LA), alpha-linolenic acid (alpha-LNA), arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA)] influenced cell growth and the responses of the cells to the chemotherapeutic agents doxorubicin (DRN), dexamethasone (DEX) and mitomycin-C (MTC). Cell proliferation generally decreased following modification with highly unsaturated fatty acids (> 10 microM). The effects of drugs on growth varied with the type of fatty acid. Preincubation with alpha-LNA enhanced survival of L5178Y cells exposed to DRN. Modification with AA, EPA or DHA (> 10 microM) reduced cell proliferation, particularly when cells were subsequently exposed to 50 or 100 nM DRN. There was no consistent relationship between fatty acid chain length, degree of unsaturation, and survival of cells when exposed to DEX or MTC. The data showed that modification of cultured L5178Y cells with highly unsaturated fatty acids, particularly DHA, enhances the toxic action of chemotherapeutic agents.
Lipids Research Group, University of California, Davis 95616.
J E
JE
Kinsella
J M
JM
Black
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D007940:Leukemia L5178 / Q000188:drug therapy / Q000473:pathology*; D051379:Mice; D008811:Mice, Inbred DBA; D016685:Mitomycin / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D005231:Fatty Acids, Unsaturated; D016685:Mitomycin; D003907:Dexamethasone