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Cancer and Metastasis Reviews

, Volume 30, Issue 3–4, pp 409–417 | Cite as

Prostaglandin catabolic enzymes as tumor suppressors

  • Hsin-Hsiung TaiEmail author
Article

Abstract

15-Hydroxyprostaglandin dehydrogenase (15-PGDH) is a key prostaglandin catabolic enzyme catalyzing the oxidation and inactivation of prostaglandin E2 (PGE2) 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 PGE2 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 E2 is catalyzed by 15-keto-prostaglandin-∆13-reductase (13-PGR), which also exhibits LTB4-12-hydroxydehydrogenase (LTB4-12-DH) activity. 13-PGR/LTB4-12-DH behaves as a tumor suppressor as well. This review summarizes current knowledge of the expression and function of 15-PGDH and 13-PGR/LTB4-12-DH in lung and other tissues during tumor progression. Future directions of research on these prostaglandin catabolic enzymes as tumor suppressors are also discussed.

Keywords

Prostaglandin dehydrogenase Prostaglandin reductase Cyclooxygenase Prostanoids Tumor suppressor Cancer chemoprevention 

Notes

Acknowledgment

I thank the support of the National Institutes of Health (HL-46296) and the Kentucky Lung Cancer Research Program for our work cited in this review.

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© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Department of Pharmaceutical Sciences, College of PharmacyUniversity of KentuckyLexingtonUSA

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