Involvement of 5-lipoxygenase in programmed cell death of cancer cells

We investigated the involvement of 5-lipoxygenase activity in the early phases of programmed cell death (PCD) induced by H2O2 or retinoids in different human tumour cells (erythroleukaemia, neuroblastoma, melanoma). Apoptotic cells showed enhanced 5-lipoxygenase activity which was paralleled by decreased superoxide dismutase activity and increased light emission. Ultraweak luminescence, mainly due to membrane lipid peroxidation by lipoxygenase activation, increased in all cell lines tested within 10-15 min after induction of PCD, in a concentration and time-dependent manner. At the same time, we observed a significant increase in the intracellular steady state level of the 5-lipoxygenase metabolite leukotriene B-4. Furthermore, 5-lipoxygenase metabolite 5-hydroxyeicosatetraenoic acid was able to induce PCD in all cell lines tested. Conversely, the general lipoxygenase inhibitor nordihydroguaiaretic acid and the selective 5-lipoxygenase inhibitor caffeic acid protected the different tumour cells from H2O2-induced PCD to a similar extent. These results show the activation of the 5-lipoxygenase pathway in PCD of three different cancer cell lines.