The mode of cell death in H-358 lung cancer cells cultured with inhibitors of 5-lipoxygenase or the free radical spin trap, NTBN.
The 5-lipoxygenase inhibitors SC41661A and MK886 with different mechanisms of action and the free radical spin trap, NTBN inhibit proliferation of the human bronchiolar lung cancer cell line NCI H-358 (5807 CRL). With continued culture, the agents induced a form of programmed cell death in which DNA laddering was not detected and ultrastructural changes were not characteristic of classic 'type 1' cellular suicide. The changes were more consistent with a type 2 cytosolic, autophagic form of PCD. MK886 induced strikingly abnormal mitochondrial morphology. Since the lipoxygenase inhibitors and NTBN induce classic type 1 PCD in U937 monoblastoid cells, these agents can activate either pathway, depending upon cell type. It is not certain whether activation of type 1 or 2 pathways depends entirely upon cell lineage and/or initiating agent, if all cells retain both pathways, and if type 1 PCD a more effective mediator of the process. These are all relevant questions for assessing the impact of PCD on malignant cell survival and considering ways in which it might be enhanced.
Ou
D
D
Department of Pathology, University of Illinois at Chicago; 60612, USA.
Bonomi
P
P
Jao
W
W
Jadko
S
S
Harris
J E
JE
Anderson
K M
KM
D000577:Amides / Q000494:pharmacology; D016923:Cell Death; D002455:Cell Division / Q000187:drug effects; D003497:Cyclic N-Oxides; D005434:Flow Cytometry; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008175:Lung Neoplasms / Q000473:pathology* / Q000648:ultrastructure; D009589:Nitrogen Oxides / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D013113:Spin Labels; D014407:Tumor Cells, Cultured; D002722:Chlorobenzenes
D000577:Amides; D003497:Cyclic N-Oxides; D007211:Indoles; D016859:Lipoxygenase Inhibitors; D009589:Nitrogen Oxides; D011725:Pyridines; D013113:Spin Labels; C060893:MK-886; D002722:Chlorobenzenes; C081292:SC 41661A; C029217:phenyl-N-tert-butylnitrone