Cytosolic phospholipase A2 and lipoxygenase are involved in cell cycle progression in neuroblastoma cells.
Arachidonic acid has been implicated in regulating cellular proliferation, and is preferentially released by the 85-kDa cytosolic phospholipase A2 (cPLA2). Recently, we demonstrated that cPLA2 is activated at distinct periods during the ongoing cell cycle of neuroblastoma cells. The purpose of the present study was to establish the role of these cPLA2 activity peaks in cell cycle progression. Inhibition of cPLA2 activity with arachidonyl trifluoromethylketone (ATK) in early G1 phase reduced DNA synthesis markedly. A 24-h incubation with ATK revealed no significant difference in cell number compared to untreated cells, although cPLA2 activity was still inhibited. This suggests redundancy of different PLA2 enzymes. Lipoxygenase inhibition in early G1 resulted in G1 phase arrest, whereas inhibitors for cyclooxygenase had no effect. Furthermore, cells stopped progressing through S phase when lipoxygenase was inhibited in early S phase, demonstrating the requirement of lipoxygenase products for S phase progression.
van Rossum
G S A T
GS
Department of Molecular Cell Biology, Institute of Biomembranes, Utrecht University, The Netherlands.
Bijvelt
J J M
JJ
van den Bosch
H
H
Verkleij
A J
AJ
Boonstra
J
J
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D019925:Cyclin A / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism*; D004247:DNA / Q000096:biosynthesis; D003576:Electron Transport Complex IV / Q000037:antagonists & inhibitors / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016193:G1 Phase / Q000187:drug effects; D008084:Lipoxygenase / Q000378:metabolism*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D009637:Masoprocol / Q000494:pharmacology; D051379:Mice; D009447:Neuroblastoma / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism*; D054467:Phospholipases A2; D016196:S Phase / Q000187:drug effects; D014407:Tumor Cells, Cultured
D019925:Cyclin A; D004791:Enzyme Inhibitors; D016859:Lipoxygenase Inhibitors; D009637:Masoprocol; D004247:DNA; D008084:Lipoxygenase; D003576:Electron Transport Complex IV; D010741:Phospholipases A; D054467:Phospholipases A2