15-Lipoxygenase-1 induces lipid peroxidation and apoptosis, and improves survival in rat malignant glioma.

ABSTRACT

BACKGROUND: Previous studies suggest either an anti- or pro-apoptotic role for 15-lipoxygenase-1 in carcinogenesis. MATERIALS AND METHODS: We used adenovirus gene transfer of human 15-lipoxygenase-1 to characterize its effects in vitro and in vivo. RESULTS: 15-Lipoxygenase-1 expression in mouse macrophages resulted in a significant, 25-fold, induction in the production of the specific 15-lipoxygenase-1 product 13-hydroxyoctadecadienoic acid. Tail vein gene transfers in mice led to highest expression of the transduced 15-lipoxygenase-1 in liver and spleen. In the liver, 15-lipoxygenase-1 significantly increased lipid peroxidation by 3.5-fold and 2-fold, three and seven days after transduction, respectively. A significant 32-fold induction in caspase-3 activity was detected in 15-lipoxygenase-1 expressing livers seven days after transduction. In a syngeneic rat model of malignant glioma, 15-lipoxygenase-1 extended survival significantly (p=0.001). CONCLUSION: Our results support the pro-apoptotic role of 15-lipoxygenase-1 and suggest that 15-lipoxygenase-1 could be a potential new target gene for the therapy of malignant glioma.