Effect of docosahexaenoic acid on rate of differentiation of HL-60 human leukemia.
We have utilized an experimental model of cell lipid modification that allows study of the effect of a polyunsaturated fatty acid on the linked processes of cellular differentiation and growth arrest. HL-60 human leukemia cells were grown in media supplemented with 10 microM concentrations of the fatty acid docosahexaenoic acid (22:6) or oleic acid (18:1) or in unsupplemented media. Gas chromatographic analysis of phospholipid extracts from HL-60 cells grown in unmodified or 18:1-supplemented media revealed 39% and 36% 18:1, 13 and 12% polyenoics, and 2 and 3% 22:6, respectively. In contrast, cells from 22:6-supplemented cultures had 22% 18:1, 18% total polyunsaturated fatty acids, and 10% 22:6. Retinoic acid was added to cells grown in the various media, and phorbol ester-induced superoxide generation, nitroblue tetrazolium reduction, and growth arrest were determined as measures of differentiation. Unmodified and 18:1-enriched cells showed inducible oxidative burst activity beginning at 48 h after the addition of retinoic acid and continuing to increase for 5 days. In marked contrast, the 22:6-enriched leukemia cells exhibited an increased oxidative activity as early as 24 h which is equivalent to about one division cycle time. G1/0-specific growth arrest was associated with the oxidative phenotypic differentiation in all three cell types. However, cells enriched with 22:6 demonstrated early growth arrest and differentiation considerably in advance of 18:1-modified or unmodified cells. An effect on the cellular differentiation process could be detected after even a brief 1-h exposure of the cells to 22:6. Therefore, a highly polyunsaturated fatty acid which is actively incorporated into membrane structures appreciably accelerates the differentiation process of this human neoplastic cell.
Burns
C P
CP
Department of Medicine, University of Iowa College of Medicine, Iowa City 52242.
Petersen
E S
ES
North
J A
JA
Ingraham
L M
LM
D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D005227:Fatty Acids / Q000032:analysis; D006801:Humans; D007700:Kinetics; D015473:Leukemia, Promyelocytic, Acute; D010743:Phospholipids / Q000032:analysis; D013481:Superoxides / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000166:cytology* / Q000187:drug effects
D005227:Fatty Acids; D010743:Phospholipids; D013481:Superoxides; D004281:Docosahexaenoic Acids; D014212:Tretinoin