Abstract
We studied the effect of specific inhibitors of 5- and 12-lipoxygenases as well as the product of cyclooxygenase activity, prostaglandin E2 , on proliferation and death of P388 leukemia cells. Inhibition of 5- and 12-lipoxygenases in the cells inhibits proliferation and induces apoptosis. The concentrations of baicalein, an inhibitor of 12-lipoxygenase, and AA861, an inhibitor of 5-lipoxygenase, causing a 50% death rate (LC50) proved to be the same, 50 μM. Excessive prostaglandin also inhibited proliferation of the cells and induced apoptosis. The LC50 for prostaglandin E2 was 4 μM. The obtained data suggest that apoptosis in P388 cells after lipoxygenase inhibition can be induced by both deficiency of lipoxygenase products and excess of prostaglandins in the cell.
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REFERENCES
Ara, G. and Teicher, B.A., Cyclooxygenase and Lipoxygenase Inhibitors in Cancer Therapy, Prostaglandins Leukot. Essent. Fatty Acids, 1996, vol. 54, pp. 3-16.
Bailey, J.M., Bryant, R.W., Low, C.E., Pupillo, M.B., and Vanderhoek, J.Y., Regulation of T-Lymphocyte Mitogenesis by the Leukocyte Product 15-Hydroxyeicosatetraenoic Acid (15-HETE), Cell. Immunol., 1982, vol. 67, pp. 112-120.
Brawley, O.W. and Thompson, I.M., Chemoprevention of Prostate Cancer, Urology, 1994, vol. 43, pp. 594-599.
Furuta, Y., Hall, E., and Sanduja, S., Prostaglandin Production by Murine Tumours as a Production for Therapeutic Response to Indomethacin, Cancer Res., 1988, vol. 48, pp. 3002-3006.
Ghosh, J. and Myers, C.E., Inhibition of Arachidonate 5-Lipoxygenase Triggers Massive Apoptosis in Human Prostate Cancer Cells, Proc. Natl. Acad. Sci. USA, 1998, vol. 95, pp. 13 182-13 187.
Giovannucci, E., Rimm, E.B., Colditz, G.A., Stampfer, M.J., Ascherio, A., Chute, C.C., and Willett, W.C., A Prospective Study of Dietary Fat and Risk of Prostate Cancer, J. Natl. Cancer Inst., 1993, vol. 85, pp. 1571-1579.
Goetzl, E.J., An, S., and Zeng, L., Specific Suppression by Prostaglandin E2 of Activation-Induced Apoptosis of Human CD4 + CD8 + T Lymphoblasts, J. Immunol., 1995, vol. 154, pp. 1041-1047.
Kang, L.T. and Vanderhoek, J.Y., Characterization of Specific Subcellular 15-Hydroxyeicosatetraenoic Acid (15-HETE) Binding Sites on Rat Basophilic Leukemia Cells, Biochim. Biophys. Acta, 1995, vol. 1256, pp. 297-304.
Korystov, Yu.N., Shaposhnikova, V.V., Levitman, M.Kh., Kudryavtsev, A.A., Kublik, L.N., Narimanov, A.A., and Orlova, O.E., The Effect of Inhibitors of Arachidonic Acid Metabolism on Proliferation and Dearth of Tumor Cells, FEBS Lett., 1998, vol. 431, pp. 224-226.
Krutetskaya, Z.I. and Lebedev, O.E., Arachidonic Acid and Its Products: The Pathways of Its Formation and Metabolism in Cells, Tsitologiya, 1993, vol. 35, pp. 3-35.
Lim, H., Paria, B.C., Das, S.K., Dinchuk, J.E., Langenbach, R., Trzaskos, J.M., and Dey, S.K., Multiple Female Reproductuve Failures in Cyclooxygenase 2-Deficient Mice, Cell, 1997, vol. 91, pp. 197-208.
Moncada, S., Gryglewski, R.J., Bunting, S., and Vane, J.R., A Lipid Peroxide Inhibits the Enzyme in Blood Vessel Microsomes That Generates from Prostaglandin Endoperoxides the Substance (Prostaglandin X) Which Prevents Platelet Aggregation, Prostaglandins, 1976, vol. 12, pp. 715-737.
Noguchi, M., Kitagawa, H., Miyazaki, I., and Mizukami, Y., Influence of Esculetin on Incidence, Proliferation, and Cell Kinetics of Mammary Carcinomas Induced by 7,12-Dimethylbenz[a]antracene in Rats on High and Low-Fat Diet, Jpn. J. Cancer Res., 1993, vol. 84, pp. 1010-1014.
Profita, M., Sala, A., Riccobono, L., Pace, E., Paterno, A., Zarini, S., Siena, L., Mirabella, A., Bonsigbore, G., and Vignola, A.M., 15(S)-HETE Modulates LTB4 Production and Neutrophil Chemotaxis in Chronic Bronchitis, Am. J. Physiol. Cell. Phisiol., 2000, vol. 279, pp. 1249-1258.
Shureiqi, I., Chen, D., Lee, J.J., Yang, P., Newman, R.A., Brenner, D.E., Lotan, R., Fischer, S.M., and Lippman, S.M., 15-LOX-1: A Novel Molecular Target of Nonsteroidal Anti-inflammatory Drug-Induced Apoptosis in Colorectal Cancer Cells, J. Nat. Cancer. Inst., 2000, vol. 92, pp. 1136-1142.
Snyder, D.S., Castro, R., and Desforges, J.F., Antiproliferative Effects of Lipoxygenase Inhibitors on Malignant Human Hematopoietic Cell Lines, Exp. Hematol., 1989, vol. 17, pp. 6-9.
Tang, D.G., Renaud, C., Stojakovic, S., Diglio, C.A., Porter, A., and Honn, K.V., 12(S)-HETE Is a Mitogenic Factor for Microvascular Endothelial Cells: Its Potential Role in Angiogenesis, Biochem. Biphys. Res. Commun., 1995, vol. 211, pp. 462-468.
Vanderhoek, J.Y. and Bailey, J.M., Activation of a 15-Lypoxygenase, Leukotriene Pathway in Human Polymorphonuclear Leucocytes by the Anti-Inflammatory Agent Ibuprofen, J. Biol. Chem., 1984, vol. 259, pp. 6752-6756.
West, D.W., Slatteryt, M.L., Robison, L.M., French, T.K., and Mahoney, A.W., Adult Dietary Intake and Prostate Cancer Risk in Utah: A Cause Control Study with Special Emphasis on Aggressive Tumor, Cancer Causes Control, 1991, vol. 2, pp. 85-94.
Young, M.R., Eicosanoids and the Immunology of Cancer, Cancer Metast. Rev., 1994, vol. 13, pp. 337-348.
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Grichenko, O.E., Shaposhnikova, V.V., Kudryavtsev, A.A. et al. Apoptosis in P388 Leukemia Cells Induced by Specific Inhibitors of 5- and 12-Lipoxygenase and the Product of Cyclooxygenase, Prostaglandin E2 . Biology Bulletin 31, 221–225 (2004). https://doi.org/10.1023/B:BIBU.0000030141.78751.90
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DOI: https://doi.org/10.1023/B:BIBU.0000030141.78751.90