Anti-tumor effects of prostaglandin D2 and its metabolites, 15-deoxy-Δ12, 14-PGJ2, by peroxisome proliferator-activated receptor (PPAR) γ-dependent and -independent pathways.

Abstract

Hematopoietic prostaglandin (PG) D synthase (H-PGDS) is known as key enzyme in the production of PGD 2 and its J series metabolite, 15-deoxy-∆ 12, 14 -PGJ 2 (15d-PGJ 2 ), is thought to play an important role for anti-inflammatory effects. Anti-tumor effects of 15d-PGJ 2 has been shown to be involved in both peroxisome proliferator-activated receptor (PPAR) γ independent and dependent pathways. The independent pathway includes the repression of the telomerase reverse transcriptase (TERT) and cyclooxygenase (COX)-2 via the down-regulation of NFκB. The dependent pathway included repression of the vascular endothelial growth factor (VEGF) receptors and COX-2 with down-regulation of NFκB, followed by the activation of PPAR γ.In this review, we focused on the role of 15d-PGJ 2 in anti-tumor effects including our evaluation in mouse bladder carcinoma model.

Mast Cell–Derived Prostaglandin D2 Inhibits Colitis and Colitis-Associated Colon Cancer in Mice

“…A degrading product of PGD 2 , 15d-PGJ 2 , also can diminish colitis in mice and have antitumor effects by activating PPARg or inhibiting NF-kB signaling (11,39). PGD 2 signaling may thus interact with such anti-inflammatory signaling and control colitis/CAC.…”