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Prostaglandin catabolic enzymes as tumor suppressors

Hsin-Hsiung Tai1

  • 1Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA. htai1@uky.edu

Cancer Metastasis Reviews
|October 25, 2011
PubMed

Insights

15-Hydroxyprostaglandin dehydrogenase (15-PGDH) and 13-keto-prostaglandin-∆(13)-reductase (13-PGR) are key tumor suppressor enzymes. Their down-regulation in cancer elevates prostaglandin E2 (PGE2) levels, promoting tumor growth.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • 15-Hydroxyprostaglandin dehydrogenase (15-PGDH) catabolizes prostaglandin E2 (PGE2), a pro-tumorigenic mediator.
  • 15-PGDH acts as a tumor suppressor by antagonizing the oncogenic COX-2 pathway.
  • Reduced 15-PGDH expression is observed in many tumors, leading to increased PGE2 levels.

Purpose of the Study:

  • To review the expression and function of 15-PGDH and 13-keto-prostaglandin-∆(13)-reductase (13-PGR) in tumor progression.
  • To discuss the role of these enzymes as tumor suppressors.
  • To highlight potential therapeutic strategies involving these enzymes for cancer chemoprevention.

Main Methods:

  • Literature review of studies on 15-PGDH and 13-PGR in cancer.
  • Analysis of molecular mechanisms regulating 15-PGDH expression, including transcriptional repression and epigenetic silencing.
  • Examination of the reciprocal regulation between 15-PGDH and COX-2 in cancer cells.

Main Results:

  • 15-PGDH and 13-PGR function as tumor suppressors by reducing pro-tumorigenic prostaglandins.
  • Tumorigenesis is associated with down-regulation of 15-PGDH and 13-PGR.
  • Agents that up-regulate 15-PGDH show promise for cancer chemoprevention.

Conclusions:

  • 15-PGDH and 13-PGR are critical regulators of prostaglandin metabolism with significant tumor-suppressive roles.
  • Targeting these enzymes offers a potential avenue for cancer prevention and therapy.
  • Further research into the regulation and therapeutic application of these enzymes is warranted.

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