Microsomal prostaglandin E synthase-1 and 5-lipoxygenase: potential drug targets in cancer.
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.
Rådmark
O
O
Department of Medical Biochemistry and Biophysics, Division of Physiological Chemistry II, Karolinska Institutet, Stockholm, Sweden.
Samuelsson
B
B
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001094:Arachidonate 5-Lipoxygenase / Q000502:physiology; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D017353:Gene Deletion; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D016859:Lipoxygenase Inhibitors; D051379:Mice; D008861:Microsomes / Q000201:enzymology; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D000071876:Prostaglandin-E Synthases
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D016859:Lipoxygenase Inhibitors; D001094:Arachidonate 5-Lipoxygenase; D019746:Intramolecular Oxidoreductases; C000605862:PTGES protein, human; D000071876:Prostaglandin-E Synthases; C000605865:Ptges protein, mouse