Activation of different lipoxygenase isozymes induces apoptosis in human erythroleukemia and neuroblastoma cells.
We investigated the ability of different hydroperoxides generated by lipoxygenase isozymes to induce programmed cell death (PCD) in human cells. Erythroleukemia K562 and neuroblastoma CHP100 cells were used, because they showed high basal activity of lipoxygenase. The hydroperoxides generated by 5-, 12-, or 15-lipoxygenases from linoleate, linolenate, or arachidonate, and the corresponding hydroxides, were able to induce PCD in both cell types, in a concentration- and time-dependent manner. After 24 h, K562 and CHP100 cells showed 2.5- to 3.5-fold more apoptotic bodies than the untreated controls. PCD elicited by lipoxygenase products was independent of intracellular glutathione concentration, and did not require mRNA transcription or protein synthesis. On the other hand, lipoxygenase products evoked an immediate and sustained rise in cytoplasmic calcium (within seconds), followed by mitochondrial uncoupling (within hours). Unlike the hydro(pero)xides, the terminal products of the arachidonate cascade (i.e., leukotrienes, prostaglandins and thromboxane) were not cytotoxic.
Maccarrone
M
M
Department of Experimental Medicine and Biochemical Sciences, IDI-IRCCS Biochemistry Laboratory, University of Rome Tor Vergata, Italy.
Ranalli
M
M
Bellincampi
L
L
Salucci
M L
ML
Sabatini
S
S
Melino
G
G
Finazzi-Agrò
A
A
D017209:Apoptosis / Q000187:drug effects; D016718:Arachidonic Acid / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005978:Glutathione / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D020014:K562 Cells; D004915:Leukemia, Erythroblastic, Acute / Q000201:enzymology* / Q000473:pathology*; D015289:Leukotrienes / Q000494:pharmacology; D019787:Linoleic Acid / Q000378:metabolism; D008054:Lipid Peroxides / Q000378:metabolism / Q000494:pharmacology; D008084:Lipoxygenase / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009447:Neuroblastoma / Q000201:enzymology* / Q000473:pathology*; D011453:Prostaglandins / Q000494:pharmacology; D013929:Thromboxane B2 / Q000494:pharmacology; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014475:Uncoupling Agents / Q000378:metabolism / Q000494:pharmacology; D017962:alpha-Linolenic Acid / Q000378:metabolism
D007527:Isoenzymes; D015289:Leukotrienes; D008054:Lipid Peroxides; D011453:Prostaglandins; D014475:Uncoupling Agents; D017962:alpha-Linolenic Acid; D016718:Arachidonic Acid; D013929:Thromboxane B2; D019787:Linoleic Acid; D008084:Lipoxygenase; D005978:Glutathione; D002118:Calcium