Inhibition of 5-lipoxygenase triggers apoptosis in pancreatic cancer cells

Oncol Rep. 2015 Feb;33(2):661-8. doi: 10.3892/or.2014.3650. Epub 2014 Dec 5.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology*
  • Adult
  • Aged
  • Apoptosis
  • Arachidonate 5-Lipoxygenase / genetics*
  • Arachidonate 5-Lipoxygenase / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Female
  • Humans
  • Hydroxyurea / analogs & derivatives*
  • Hydroxyurea / pharmacology
  • Lipoxygenase Inhibitors / pharmacology*
  • Lymphatic Metastasis / genetics
  • Lymphatic Metastasis / pathology
  • Male
  • Middle Aged
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology*

Substances

  • Lipoxygenase Inhibitors
  • Arachidonate 5-Lipoxygenase
  • ALOX5 protein, human
  • zileuton
  • Hydroxyurea