Polyunsaturated fatty acids induce cell death in YAC-1 lymphoma by a caspase-3-independent mechanism.
BACKGROUND
The involvement of certain fatty acids in the induction of apoptosis has been established recently. In fact, considerable attention has been given in the past few years to the participation of polyunsaturated fatty acids as substances capable of modulating tumor cell growth.


METHODS
Fatty acids such as eicosapentaenoic acid (EPA), linolenic acid (LNA), arachidonic acid (AA), linoleic acid (LA), oleic acid (OA) or stearic acid (SA) were added to YAC-1 tumor cells.


RESULTS
Incubation of cells with fatty acids revealed a loss of cell viability in a dose-dependent manner. Quantification of DNA fragmentation showed a significant increase particularly in cells treated in the presence of LA, whereas the accumulation of triacylglycerols in the form of cytoplasmic lipid droplets was significantly enhanced in cells cultured with EPA, LNA or AA. The production of reactive oxygen species (ROS) was substantially increased after cell incubation. Nevertheless, the analysis of caspase-3 activity indicated a relevant increase in cells cultured in the presence of LA, OA or SA, but not in cells cultured with EPA, LNA or AA.


CONCLUSIONS
On the basis of these results, we can speculate that long-chain polyunsaturated fatty acids such as EPA and AA as well as LNA induce cell death in YAC-1 lymphoma by an independent mechanism of caspase-3 activation.
Puertollano
Maria A
MA
Department of Health Sciences, Faculty of Experimental Sciences, University of Jaén, E-23071, Jaén, Spain.
de Pablo
Manuel A
MA
Alvarez de Cienfuegos
Gerardo
G
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects / Q000502:physiology; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D005456:Fluorescent Dyes; D008223:Lymphoma / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D008563:Membrane Lipids / Q000378:metabolism; D051379:Mice; D009930:Organic Chemicals; D010078:Oxazines; D017382:Reactive Oxygen Species / Q000378:metabolism
D005231:Fatty Acids, Unsaturated; D005456:Fluorescent Dyes; D008563:Membrane Lipids; D009930:Organic Chemicals; D010078:Oxazines; D017382:Reactive Oxygen Species; C402795:SYTOX Green; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases; C044808:nile red