Microsomal prostaglandin E synthase-1 and 5-lipoxygenase: potential drug targets in cancer

J Intern Med. 2010 Jul;268(1):5-14. doi: 10.1111/j.1365-2796.2010.02246.x. Epub 2010 Apr 28.

Abstract

There is strong evidence for a role of prostaglandin (PG)E(2) in cancer cell proliferation and tumour development. In PGE(2) biosynthesis, cyclooxygenases (COX-1/2) convert arachidonic acid to PGH(2), which can be isomerized to PGE(2) by PGE synthases, including microsomal PGE synthase-1 (MPGES-1). Data describing genetic deletions of MPGES-1 are reviewed. The results suggest that MPGES-1 is an alternative therapeutic target for cancer cells and tumours that express this enzyme. Several compounds that target COX-2 or MPGES-1 also inhibit 5-lipoxygenase. This may be advantageous for treatment of some forms of cancer.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Arachidonate 5-Lipoxygenase / physiology
  • Enzyme Inhibitors / therapeutic use*
  • Gene Deletion
  • Humans
  • Intramolecular Oxidoreductases / antagonists & inhibitors*
  • Intramolecular Oxidoreductases / genetics
  • Intramolecular Oxidoreductases / physiology
  • Lipoxygenase Inhibitors*
  • Mice
  • Microsomes / enzymology
  • Neoplasms / drug therapy*
  • Neoplasms / enzymology
  • Neoplasms / genetics
  • Prostaglandin-E Synthases

Substances

  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Lipoxygenase Inhibitors
  • Arachidonate 5-Lipoxygenase
  • Intramolecular Oxidoreductases
  • PTGES protein, human
  • Prostaglandin-E Synthases
  • Ptges protein, mouse