Prostaglandin catabolic enzymes as tumor suppressors.
15-Hydroxyprostaglandin dehydrogenase (15-PGDH) is a key prostaglandin catabolic enzyme catalyzing the oxidation and inactivation of prostaglandin E(2) (PGE(2)) synthesized from the cyclooxygenase (COX) pathway. Accumulating evidence indicates that 15-PGDH may function as a tumor suppressor antagonizing the action of COX-2 oncogene. 15-PGDH has been found to be down-regulated contributing to elevated levels of PGE(2) in most tumors. The expression of 15-PGDH and COX-2 appears to be regulated reciprocally in cancer cells. Down-regulation of 15-PGDH in tumors is due, in part, to transcriptional repression and epigenetic silencing. Numerous agents have been found to up-regulate 15-PGDH by down-regulation of transcriptional repressors and by attenuation of the turnover of the enzyme. Up-regulation of 15-PGDH may provide a viable approach to cancer chemoprevention. Further catabolism of 15-keto-prostaglandin E(2) is catalyzed by 15-keto-prostaglandin-∆(13)-reductase (13-PGR), which also exhibits LTB(4)-12-hydroxydehydrogenase (LTB(4)-12-DH) activity. 13-PGR/LTB(4)-12-DH behaves as a tumor suppressor as well. This review summarizes current knowledge of the expression and function of 15-PGDH and 13-PGR/LTB(4)-12-DH in lung and other tissues during tumor progression. Future directions of research on these prostaglandin catabolic enzymes as tumor suppressors are also discussed.
Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA. htai1@uky.edu
Hsin-Hsiung
HH
Tai
D011452:15-Oxoprostaglandin 13-Reductase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006911:Hydroxyprostaglandin Dehydrogenases / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000628:therapy; D011453:Prostaglandins / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
D011453:Prostaglandins; D025521:Tumor Suppressor Proteins; D006911:Hydroxyprostaglandin Dehydrogenases; C035859:15-hydroxyprostaglandin dehydrogenase; D051546:Cyclooxygenase 2; D011452:15-Oxoprostaglandin 13-Reductase