Expression of lipoxygenase in human bladder carcinoma and growth inhibition by its inhibitors

The metabolism of arachidonic acid by the cyclooxygenase or lipoxygenase pathway generates eicosanoids, which have been implicated in the pathogenesis of various human diseases, including cancer. They are now believed to have important roles in tumor promotion, progression and metastasis. The involvement of lipoxygenase expression and function in tumor growth and metastasis has been reported in human tumor cell lines.

The expression of 5 and 12-lipoxygenase in patients with bladder tumor and chronic cystitis, and in normal bladder tissues was examined. We also examined the effects of their inhibitors on cell proliferation in a bladder cancer cell line. The expression of 5 and 12-lipoxygenase protein was detected by immunohistochemistry. The effects of lipoxygenase inhibitors on bladder cancer cell growth were examined by MTT (3-[4,5-dimethylthiazol-2-thiazolyl]-2,5-diphenyltetrazolium bromide) assay, while Hoechst (Sigma Chemical Co., St. Louis, Missouri) staining was used to determine whether lipoxygenase inhibitors induce apoptosis.

While slight 5 and 12-lipoxygenase expression was detected in chronic cystitis and normal bladder tissues, marked 5 and 12-lipoxygenase expression was detected in bladder cancer tissues. Lipoxygenase inhibitors caused marked inhibition of bladder cancer cells in a concentration and time dependent manner. Cells treated with lipoxygenase inhibitors showed chromatin condensation, cellular shrinkage, small membrane bound bodies (apoptotic bodies) and cytoplasmic condensation.

Lipoxygenase is induced in bladder cancer. Results suggest that lipoxygenase inhibitors may mediate potent antiproliferative effects against bladder cancer cells. Thus, lipoxygenase may become a new target in the treatment of bladder tumors.