The mode of cell death in H-358 lung cancer cells cultured with inhibitorsof 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 continu ed culture, the agents induced a form of programmed cell death in which DNA laddering was not detected and ultrastructural changes were not characteri stic 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 NT BN induce classic type 1 PCD in U937 monoblastoid cells, these agents can a ctivate 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 f or assessing the impact of PCD on malignant cell survival and considering w ays in which it might be enhanced. (C) 2001 Elsevier Science Ireland Ltd. A ll rights reserved.