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15-Hydroxyprostaglandin dehydrogenase as a novel molecular target for cancer chemoprevention and therapy

Cited 36 time in Web of Science Cited 35 time in Scopus
Issue Date
2011-11
Citation
Biochemical Pharmacology, Vol.82 No.10, pp.1352-1360
Keywords
15-Hydroxyprostaglandin dehydrogenase (15-PGDH)Tumor suppressorChemopreventionCyclooxygenase-2 (COX-2)Prostaglandin E(2) (PGE(2))
Abstract
Cyclooxygenase-2 (COX-2), a rate-limiting enzyme in arachidonic acid cascade, plays a key role in the biosynthesis of prostaglandin E(2) (PGE(2)) upon inflammatory insults. Overproduction of PGE(2) stimulates proliferation of various cancer cells, confers resistance to apoptosis of cancerous or transformed cells, and accelerates metastasis and angiogenesis. Excess PGE(2) undergoes metabolic inactivation which is catalyzed by NAD(+)-dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH). In this context, 15-PGDH has been speculated as a physiological antagonist of COX-2 and a tumor suppressor. Thus, overexpression of 15-PGDH has been known to protect against experimentally induced carcinogenesis and renders the cancerous or transformed cells susceptible to apoptosis by counteracting oncogenic action of PGE(2). In contrast, silence of 15-PGDH is observed in some cancer cells, which is associated with epigenetic modification, such as DNA methylation and histone deacetylation, in the promoter region of 15-PGDH. A variety of compounds capable of inducing the expression of 15-PGDH have been reported, which include the histone deacetylase inhibitors, nonsteroidal anti-inflammatory drugs, and peroxisome proliferator-activated receptor-gamma agonists. Therefore, 15-PGDH may be considered as a novel molecular target for cancer chemoprevention and therapy. This review highlights the role of 15-PGDH in carcinogenesis and its regulation. (C) 2011 Elsevier Inc. All rights reserved.
ISSN
0006-2952
URI
https://hdl.handle.net/10371/172610
DOI
https://doi.org/10.1016/j.bcp.2011.08.005
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Graduate School of Convergence Science and Technology (융합과학기술대학원)Dept. of Molecular and Biopharmaceutical Sciences (분자의학 및 바이오제약학과)Journal Papers (저널논문_분자의학 및 바이오제약학과)
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