Arachidonic acid metabolism in growth control of A549 human lung adenocarcinoma cells.
The role of individual eicosanoids of the arachidonic acid (AA) cascade in the growth control of A549 human lung adenocarcinoma cells has been studied. Cyclooxygenase and lipoxygenase metabolites of [14C]AA incorporated were actively synthesized in the cultures of tumor cells with full confluence unaccomplished. In such cultures inhibitors of AA metabolism (indomethacin and esculetin) and also a lipoxygenase metabolite of AA, 15-hydroxyeicosatetraenoic acid (15-HETE), significantly suppressed the incorporation of [3H]thymidine and biosynthesis of prostaglandin E2 (PGE2). Other lipoxygenase metabolites of AA (5-HETE and 12-HETE) had no effect on these parameters. The basic fibroblast growth factor (bFGF) had practically no affect on the growth of A549 cells and the PGE2 production in cultures with 5% fetal calf serum (FCS); however, in the presence of 0.5% FCS this factor significantly increased the number of tumor cells. The growth-stimulating effect of bFGF was completely abolished by a cyclooxygenase inhibitor indomethacin. The data suggest a key role of PGE2 in the growth control of A549 cells with an active synthesis of cyclooxygenase and lipoxygenase metabolites of AA, its importance in realization of the mitogenic effect of bFGF, and specific features of 15-HETE as a down-regulator of the PGE2-dependent proliferation.
Kudryavtsev
I A
IA
Institute of Carcinogenesis, Blokhin Russian Cancer Research Center, Russian Academy of Medical Sciences, Moscow, 115478, Russia. kudria@crc.umos.ru
Golenko
O D
OD
Gudkova
M V
MV
Myasishcheva
N V
NV
D000230:Adenocarcinoma / Q000378:metabolism*; D001095:Arachidonic Acids / Q000378:metabolism*; D002250:Carbon Radioisotopes; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D015237:Dinoprost / Q000096:biosynthesis; D015232:Dinoprostone / Q000096:biosynthesis; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000096:biosynthesis / Q000737:chemistry / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008175:Lung Neoplasms / Q000378:metabolism*; D013936:Thymidine / Q000737:chemistry / Q000378:metabolism; D014316:Tritium; D014407:Tumor Cells, Cultured; D014468:Umbelliferones / Q000494:pharmacology
D001095:Arachidonic Acids; D002250:Carbon Radioisotopes; D016861:Cyclooxygenase Inhibitors; D006893:Hydroxyeicosatetraenoic Acids; D014468:Umbelliferones; D014316:Tritium; D016222:Fibroblast Growth Factor 2; D004247:DNA; D015237:Dinoprost; D015232:Dinoprostone; C007628:esculetin; D013936:Thymidine; D007213:Indomethacin