Cysteinyl-leukotriene1 receptor is a potent target for the prevention and treatment of human urological cancer.

Abstract

Leukotrienes (LTs) are biologically active fatty acids derived from the oxidative metabolism of arachidonic acid through the 5-lipoxygenase pathway. LTs work to contract airway smooth muscle, increase vascular permeability and mucus secretions, and attract and activate inflammatory cells in the airways of patients with asthma. Recently, it was reported that the LTD4 receptor (cysteinylLT1 receptor; CysLT1R) plays an important role in carcinogenesis. In this study, CysLT1R expression was examined in human urological cancer cell lines (renal cell carcinoma, bladder cancer, prostate cancer and testicular cancer) using immunohistochemistry and RT-PCR. The effect of CysLT1R antagonist on these cells was also examined using the MTT assay, Hoechst staining and flow cytometry. CysLT1R expression was significantly more extensive and intense in the malignant tissues than in normal tissues. Furthermore, CysLT1R antagonist induced a reduction in malignant cell viability through early apoptosis. These results demonstrate that CysLT1R expressed in urological cancer may play a crucial role in carcinogenesis. CysLT1R may therefore be a novel target in the treatment of urological cancer.