Multiplication and death-type of leukemia cell lines exposed to very long-chain polyunsaturated fatty acids

Abstract

Polyunsaturated fatty acids (PUFA) may reduce cell multiplication in cultures of normal, as well as transformed, white blood cells. We assessed the sensitivity of 14 different leukemia cell lines to PUFA by measuring cell number after 3 days of incubation. Ten of the examined cell lines were sensitive to 30, 60 and/or 120 M of arachidonic, eicosapentaenoic and docosahexaenoic acid, whereas four cell lines were resistant. The sensitivity to PUFA was not associated with any particular cell lineage, clinical origin or specific mRNA pattern of bcl-2 and c-myc. Effects on cell viability were assessed by studying cell membrane integrity, DNA fragmentation and cell morphology. The sensitive cell lines Raji and Ramos died by necrosis and apoptosis, respectively, during incubation with eicosapentaenoic acid, whereas the viability of the resistant U-698 cell line was unaffected. The effects of EPA on Raji cells, was counteracted by vitamin E, indicating that lipid peroxidation was involved. However, apoptosis induced by eicosapentaenoic acid in Ramos cells, was unaffected by vitamin E, as well as eicosanoid synthesis inhibitors. In conclusion, our results indicate that a majority of leukemia cell lines are sensitive to PUFA. This sensitivity may be caused by induction of apoptosis or necrosis by very long-chain polyunsaturated fatty acids.

Eicosapentaenoic Acid Demethylates a Single CpG That Mediates Expression of Tumor Suppressor CCAAT/Enhancer-binding Protein δ in U937 Leukemia Cells

“…Morphology of U937 Cells-Variable effects of PUFAs on proliferation, differentiation, and apoptosis in leukemia cells have been reported in relation to cell line and fatty acid concentration (9,11,12). To study the effects of fatty acids on the percent distribution in the various phases of the cell cycle, U937 cells were analyzed by flow cytometry after incubation with fatty acids of increasing carbon chain length and double bond number.…”

Effect of fatty acids on leukocyte function

“…Cell death occurs by apoptosis at concentrations close to the physiological free fatty acid concentrations, as assessed by induction of internucleosomal DNA cleavage, chromatin condensation and nuclear breakdown (37,38). Higher doses of fatty acids preferentially cause necrosis, with a rapid loss of membrane integrity, lysosomal enzyme leakage and cell swelling.…”

“…Higher doses of fatty acids preferentially cause necrosis, with a rapid loss of membrane integrity, lysosomal enzyme leakage and cell swelling. Both apoptosis and necrosis seem to be associated with oxidative stress, as they can be partially prevented by antioxidants such as tocopherol (37). As to eicosanoids, they have been found to play an important role in apoptosis depending on the cell type or treatment.…”

“…General effects -PUFAs and volatile fatty acids at high concentrations cause cell death via apoptosis or necrosis (37)(38)(39)(40).…”

Induction of apoptosis by polyunsaturated fatty acids and its relationship to fatty acid inhibition of carnitine palmitoyltransferase I activity in Hep2 cells

“…There are many studies demonstrating both saturated and unsaturated fatty acid inductions of apoptosis (10)(11)(12). Of particular interest to the evaluation of this work are the reports of the induction of apoptosis in murine cell lines by the saturated fatty acids, stearate and palrnitate, where the CPT I inhibitor etomoxir caused a marked increase in palmitateinduced apoptosis (12).…”