Inhibition of 5-lipoxygenase triggers apoptosis in pancreatic cancer cells

Abstract

The 5-lipoxygenase (5-LOX) pathway has been associated with a variety of inflammatory diseases including asthma, atherosclerosis, rheumatoid arthritis, cancer and liver fibrosis. Several classes of 5-LOX inhibitors have been identified, but only one drug, zileuton, a redox inhibitor of 5-LOX, has been approved for clinical use. In the present study, 5-LOX was found to be overexpressed not only in pancreatic cancer cell lines but also in tissue samples of patients suffering from pancreatic adenocarcinoma. There was a close correlation between the tumor expression levels of 5-LOX mRNA and protein and the clinicopathological patient characteristics including lymph node metastasis and TNM stage. Zileuton suppressed the proliferation of SW1990 cells in a concentration-and time-dependent manner. In addition, zileuton induced SW1990 cells to undergo apoptosis and significantly decreased 5-LOX expression. The number of apoptotic cells, estimated by flow cytometry, Annexin V/PI assay, TUNEL staining and sub-diploid population was significantly higher than that of the control. These results suggest that the level of 5-LOX expression was increased in pancreatic cancer tissues and may be related to lymph node metastasis and TNM stage.