Phospholipase A2-induced stimulation of A549 lung adenocarcinoma cell line proliferation.
Phospholipase A2 (PLA2) activity was found in the cytosolic fraction of the A549 human lung adenocarcinoma line. This PLA2 had a molecular mass of approximately 70 kDa as assessed by gel filtration chromatography and required submicromolar concentrations of calcium concentrations for optimal activity. These characteristics are consistent with the cytosolic PLA2 recently reported in other cell types, such as U937 cells. We have now demonstrated that A549 cell PLA2 (PLA2 activity: 1 unit/ml) partially purified by gel filtration stimulated proliferation of A549 cells by 50% after 3 days of culture. Similarly, porcine pancreatic PLA2 (0.1 unit/ml) also promoted proliferation of A549 cell cultures by 42%. Furthermore, A549 cell PLA2 stimulated prostaglandin E2 release (approx. 7-fold increase). Both PLA2s lost activity when treated with p-bromophenacyl bromide. Neither porcine pancreatic PLA2 nor A549 cell PLA2 reversed the inhibitory activities of dexamethasone and indomethacin on cell growth. These results suggest that both of these PLA2s stimulate A549 cell growth, and that this is likely to be mediated by increased eicosanoid production.
Tokumoto
H
H
Department of Biochemical Pharmacology, William Harvey Research Institute, Medical College of St. Bartholomew's Hospital, London, UK.
Croxtall
J D
JD
Choudhury
Q
Q
Flower
R J
RJ
D000098:Acetophenones / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002850:Chromatography, Gel; D003600:Cytosol / Q000201:enzymology; D003907:Dexamethasone / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D010741:Phospholipases A / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D054467:Phospholipases A2; D014407:Tumor Cells, Cultured / Q000201:enzymology*
D000098:Acetophenones; D003907:Dexamethasone; D010741:Phospholipases A; D054467:Phospholipases A2; D009543:Nifedipine; D015232:Dinoprostone; C006821:4-bromophenacyl bromide; D002118:Calcium; D007213:Indomethacin