Activation of nitric oxide synthase is involved in tamoxifen-induced apoptosis of human erythroleukemia K562 cells.
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.
Maccarrone
M
M
Department of Experimental Medicine and Biochemical Sciences, University of Rome Tor Vergata, Italy.
Fantini
C
C
Ranalli
M
M
Melino
G
G
Agrò
A F
AF
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
D004791:Enzyme Inhibitors; D013629:Tamoxifen; D009599:Nitroprusside; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester