Lipoxygenase pathway of arachidonic acid metabolism in growth control of tumor cells of different type.
The influence of inhibitors of different lipoxygenases (LOX) on the growth of human tumor cells with different profiles of synthesized eicosanoids was studied. The studied LOX inhibitors had virtually no influence on the growth of A549 cells actively synthesizing cyclooxygenase and lipoxygenase metabolites of arachidonic acid (AA). The inhibitor of 12-LOX, baicalein, significantly inhibited proliferation in cultures of A431 epidermoid carcinoma cells with a characteristic domination of the major lipoxygenase metabolite of AA, 12-hydroxyeicosatetraenoic acid (12-HETE), in the profile of synthesized eicosanoids and reduced to 70% the incorporation of [3H]thymidine into DNA. Treatment of these cultures with 12-HETE virtually restored the growth potential of the tumor cells. The findings suggest that the lipoxygenase metabolite of AA, 12-HETE, is a growth-limiting factor for tumor cells of definite type.
Kudryavtsev
I A
IA
Institute of Carcinogenesis, Blokhin Russian Cancer Research Center, Russian Academy of Medical Sciences, Moscow, 115478, Russia. kudria@crc.umos.ru
Gudkova
M V
MV
Pavlova
O M
OM
Oreshkin
A E
AE
Myasishcheva
N V
NV
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid / Q000494:pharmacology; D000230:Adenocarcinoma / Q000378:metabolism*; D001091:Arachidonate Lipoxygenases / Q000378:metabolism*; D016718:Arachidonic Acid / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D044950:Flavanones / Q000494:pharmacology; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology; D008175:Lung Neoplasms / Q000378:metabolism*; D009578:Nitrobenzenes / Q000494:pharmacology; D012457:Salicylamides / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000378:metabolism*; D014468:Umbelliferones / Q000494:pharmacology
D044950:Flavanones; D006893:Hydroxyeicosatetraenoic Acids; D009578:Nitrobenzenes; D012457:Salicylamides; D013449:Sulfonamides; D014468:Umbelliferones; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D016718:Arachidonic Acid; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; C006680:baicalein; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; C005703:salicylhydroxamic acid; D001091:Arachidonate Lipoxygenases; C007628:esculetin