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.