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Prostaglandin catabolic enzymes as tumor suppressors

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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.

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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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  1. Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY, 40536, USA

    Hsin-Hsiung Tai

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Tai, HH. Prostaglandin catabolic enzymes as tumor suppressors. Cancer Metastasis Rev 30, 409–417 (2011). https://doi.org/10.1007/s10555-011-9314-z

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