title: Activation of nitric oxide synthase is involved in tamoxifen-induced apoptosis of human erythroleukemia K562 cells.
abstract: Tamoxifen induces apoptosis (programmed cell death) in human erythroleukemia K562 cells. Nitric oxide synthase activity and expression increased in apoptotic cells by 315% and 280%, respectively, compared to controls. The specific inhibitor of nitric oxide synthase, L-NAME, protected K562 cells from tamoxifen-induced apoptosis, whereas the nitric oxide donor, sodium nitroprusside (SNP), potentiated the apoptotic effect of the drug. In addition, 5-lipoxygenase was activated by tamoxifen and the specific enzyme inhibitor, MK886, protected K562 cells against the drug. Conversely, the 5-lipoxygenase product, 5-hydroperoxyeicosatetraenoic acid, enhanced the tamoxifen-induced apoptosis. Finally, tamoxifen altered also membrane properties of K562 cells.
authors.affiliation: Department of Experimental Medicine and Biochemical Sciences, University of Rome Tor Vergata, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Maccarrone
authors.forename: C
authors.initials: C
authors.lastname: Fantini
authors.forename: M
authors.initials: M
authors.lastname: Ranalli
authors.forename: G
authors.initials: G
authors.lastname: Melino
authors.forename: A F
authors.initials: AF
authors.lastname: Agrò
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute / Q000201:enzymology / Q000473:pathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D013629:Tamoxifen / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D004791:Enzyme Inhibitors; D013629:Tamoxifen; D009599:Nitroprusside; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester