Celecoxib inhibits 5-lipoxygenase

Biochem Pharmacol. 2008 Oct 1;76(7):862-72. doi: 10.1016/j.bcp.2008.07.009. Epub 2008 Jul 19.


Celecoxib is a selective cyclooxygenase-2 (COX-2) inhibitor used in the therapy of inflammatory and painful conditions. Various COX-2-independent pharmacological effects, such as a chemo-preventive and tumor-regressive activity have been suggested, but the respective non-COX-2 targets of celecoxib are still a matter of research. We now demonstrate that celecoxib inhibits 5-lipoxygenase (5-LO), a key enzyme in leukotriene (LT) biosynthesis. Celecoxib suppressed 5-LO product formation in ionophore A23187-activated human polymorphonuclear leukocytes (IC(50) approximately 8 microM). Similarly, celecoxib inhibited LTB(4) formation in human whole blood (IC(50) approximately 27.3 microM). Direct interference of 5-LO with celecoxib was visualized by inhibition of enzyme catalysis both in cell homogenates and with purified 5-LO (IC(50) approximately 23.4 and 24.9 microM, respectively). Related lipoxygenases (12-LO and 15-LO) were not affected by celecoxib. Other COX-2 inhibitors (etoricoxib and rofecoxib) or unselective NSAIDs (non-steroidal anti-inflammatory drugs, diclofenac) failed to inhibit 5-LO. In rats which received celecoxib (i.p.), the blood LTB(4) levels were dose-dependently reduced with an ED(50) value approximately 35.2 mg/kg. Together, celecoxib is a direct inhibitor of 5-LO in vitro and in vivo. These findings provide a potential molecular basis for some of the described COX-2-independent pharmacological effects of celecoxib.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Arachidonate 5-Lipoxygenase / metabolism
  • Celecoxib
  • Cells, Cultured
  • Cyclooxygenase 2 Inhibitors / pharmacology*
  • Female
  • HeLa Cells
  • Humans
  • Hydroxyeicosatetraenoic Acids / metabolism
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / enzymology
  • Leukotriene B4 / metabolism
  • Lipoxygenase Inhibitors*
  • Male
  • Pyrazoles / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Sulfonamides / pharmacology*


  • Cyclooxygenase 2 Inhibitors
  • Hydroxyeicosatetraenoic Acids
  • Lipoxygenase Inhibitors
  • Pyrazoles
  • Sulfonamides
  • Leukotriene B4
  • 5-hydroxy-6,8,11,14-eicosatetraenoic acid
  • Arachidonate 5-Lipoxygenase
  • Celecoxib