Prostaglandin catabolic enzymes as tumor suppressors

Abstract

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.

15-Hydroxyprostaglandin Dehydrogenase-derived 15-Keto-prostaglandin E2 Inhibits Cholangiocarcinoma Cell Growth through Interaction with Peroxisome Proliferator-activated Receptor-γ, SMAD2/3, and TAP63 Proteins

“…The NAD ϩ -dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH) catalyzes the oxidation of the 15(S)-hydroxyl group of PGE 2 , converting PGE 2 into 15-keto-PGE 2 (6). Consistent with the documented catabolism of PGE 2 by 15-PGDH, accumulating evidence suggests an important role of 15-PGDH in cancer development and progression (7)(8)(9)(10)(11)(12)(13)(14)(15).…”

Identification of prostamides, fatty acyl ethanolamines, and their biosynthetic precursors in rabbit cornea

“…DH-EA and AL-EA were minor congeners (0.4 and 0.7 pg/mg tissue, respectively), indicating very low levels of DHA and ␣ -linolenic incorporation at the sn -1 position of corneal PC available for transacylation to the amine terminal of phosphatidylethanolamine (PE) ( 40 ). This is in contrast to the high levels of di-docosahexanoyl-PC and -PE species reported in rat and bovine retinal phospholipids ( 41,42 ) and highlights Finally, the presence of 13,14 dihydro 15-keto metabolites of PGE 2 and PGF 2 ␣ shows the expression of 15-prostaglandin dehydrogenase (15-PGDH) and PG keto reductases in rabbit cornea, suggesting that the tissue actively controls the levels of PGs through their metabolism and deactivation ( 38 ). Overall, these data clearly show the presence of an active arachidonic acid cascade through COX, while the PG profi le suggests the prevalence of PGIS, PGES, and PGDS isoforms in rabbit cornea, suggesting that the tissue has the capability of forming the correspondent prostamide species.…”

The proteomic response of cheliped myofibril tissue in the eurythermal porcelain crabPetrolisthes cinctipesto heat shock following acclimation to daily temperature fluctuations

“…RKIP inhibits the MEK-ERK1/2 MAP kinase module (Yeung et al, 2000;Yeung et al, 1999) and thereby the phosphorylation of phospholipase A 2 , directly inhibiting the synthesis of proinflammatory prostanoids from arachidonic acid, including prostaglandin E 2 (PGE), via cyclooxygenase (COX) and leukotrienes, such as leukotriene B 4 (LTB 4 ) via lipooxygenase (LOX). Further downstream, prostaglandin reductase (PGR), which also functions as LTB 4 DH, catabolizes PGE and LTB 4 into inactive metabolites, thereby suppressing an immune reaction and hemocyte recruitment (Marks et al, 2009;Tai, 2011). In addition to being RKIPPhosphokinase C-dependent phosphorylation (Corbit et al, 2003) (Lorenz et al, 2003) IκB kinases (IκK) IκB-NFκB (cytosol, inactive) IκB-+NFκB (nucleus, active) Proteasome degradation RAS PKA RAF 14-3-3…”