Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Eicosanoids regulate a wide spectrum of cellular processes including cell proliferation. We have shown previously that lipoxygenase metabolites of arachidonic acid modulate normal human hematopoiesis by in vitro colony assays. In this study we investigated the role of lipoxygenase metabolites in regulating the proliferation of several malignant hematopoietic cell lines, including K562 and EM-2 (chronic myelogenous leukemia blasts), HL-60 (promyelocytic leukemia cells), and U937 (malignant histiocytes). Piriprost, a specific inhibitor of 5-lipoxygenase, inhibits proliferation of these cell lines up to 95% with 50% cell inhibition at approximately 3 x 10(-5) M. Other less specific lipoxygenase inhibitors such as caffeic acid, nordihydroguaiaretic acid, and BW755C have similar activity in a [3H]-thymidine incorporation assay. In contrast, indomethacin, which is a cyclooxygenase inhibitor, has no suppressive effect in these assays. Inhibition by these drugs is completely reversible. Several nonhematopoietic malignant cell lines do not appear to be affected by these drugs. Two specific lipoxygenase metabolites, leukotriene B4 and leukotriene D4, stimulate leukemia cell line proliferation to 150% of control levels when added directly to cell cultures. These data suggest that certain lipoxygenase products, perhaps leukotrienes, are critical for the proliferation of malignant hematopoietic cells in vitro.
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PMID:Antiproliferative effects of lipoxygenase inhibitors on malignant human hematopoietic cell lines. 290 62

We studied the effect of piriprost, an inhibitor of sulfidopeptide leukotriene (LT) formation, on the generation of the known products of the 5-lipoxygenase pathway of arachidonate metabolism in calcium ionophore A23187-challenged rat basophil leukemia cells and cloned, growth factor-dependent, mouse mast cells. Piriprost inhibited the formation of 5-hydroxyeicosatetraenoic acid (5-HETE), and LTB4, and the sulfidopeptide leukotrienes (LTC4 in the mouse mast cells and both LTC4 and a mixture of LTD4 and LTE4 in the rat basophil leukemia cells) in parallel (IC50 values ranged between 9 and 14 microM for the mouse mast cells and between 15 and 50 microM for the basophil leukemia cells). Our previous observation that piriprost is only a very weak inhibitor of the solubilized LTC synthase of rat basophil leukemia cells was extended to similar enzyme preparations derived from the mouse mast cells (IC50 1.5 mM). The results are consistent with the conclusion that piriprost acts as an inhibitor of the 5-lipoxygenase reaction and that its activity in intact cells is not likely to involve the inhibition of the LTC synthase.
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PMID:Experiments on the mode of action of piriprost (U-60,257), an inhibitor of leukotriene formation in cloned mouse mast cells and in rat basophil leukemia cells. 310 73