INVOLVEMENT OF 5-LIPOXYGENASE IN PROGRAMMED CELL-DEATH OF CANCER-CELLS

We investigated the involvement of 5-lipoxygenase activity in the earl y phases of programmed cell death (PCD) induced by H2O2 or retinoids i n different human tumour cells (erythroleukaemia, neuroblastoma, melan oma). Apoptotic cells showed enhanced 5-lipoxygenase activity which wa s paralleled by decreased superoxide dismutase activity and increased light emission. Ultraweak luminescence, mainly due to membrane lipid p eroxidation by lipoxygenase activation, increased in all cell lines te sted within 10-15 min after induction of PCD, in a concentration and t ime-dependent manner. At the same time, we observed a significant incr ease in the intracellular steady state level of the 5-lipoxygenase met abolite leukotriene B-4. Furthermore, 5-lipoxygenase metabolite 5-hydr oxyeicosatetraenoic acid was able to induce PCD in all cell lines test ed. Conversely, the general lipoxygenase inhibitor nordihydroguaiareti c acid and the selective 5-lipoxygenase inhibitor caffeic acid protect ed the different tumour cells from H2O2-induced PCD to a similar exten t. These results show the activation of the 5-lipoxygenase pathway in PCD of three different cancer cell lines.