O32 Curcumin induces expression of 15-hydroxyprostaglandin dehydrogenase in normal gastric mucosa RGM-1 cells and mouse stomach in vivo: A potential role of AP-1
2017
Overproduction of prostaglandin E 2 (PGE 2 ) has been reported to be implicated in carcinogenesis. The intracellular level of PGE 2 is regulated not only by its biosynthesis, but also by the degradation process. 15-Hydroxyprostaglandin dehydrogenase (15-PGDH) is the key enzyme that catalyzes the inactivation of PGE 2 . In the present study, we found that curcumin, a yellow coloring agent present in the rhizome of Curcuma longa Linn (Zingiberaceae), induced expression of 15-PGDH at both the protein and mRNA levels in normal rat gastric mucosa cells (RGM-1). By using deletion constructs of the 15-PGDH promoter, we have found that activator protein-1 (AP-1) is the most essential transcription factor responsible for curcumin-induced upregulation of 15-PGDH expression. In addition, oral administration of curcumin increased the expression of 15-PGDH in the mouse stomach. Curcumin enhanced the expression of c-Jun and c-Fos in the nuclear fraction of RGM-1 cells and the mouse stomach in vivo . Knockdown of c- jun , a gene encoding one of the major components of AP-1, suppressed curcumin-induced expression of 15-PGDH. In addition, curcumin increased phosphorylation of ERK1/2 and JNK. Curcumin-induced 15-PGDH expression was abrogated by the pharmacological inhibition of the aforementioned kinases. In contrast, tetrahydrocurcumin which lacks the α , β -unsaturated carbonyl group failed to induce expression of 15-PGDH, suggesting that the electrophilic α , β -unsaturated carbonyl group of curcumin is essential for its induction of 15-PGDH expression in RGM-1 cells. Taken together, our study suggests that curcumin-induced upregulation of 15-PGDH in RGM-1 cells and mouse stomach through activation of AP-1 may contribute to chemopreventive effects of this phytochemical on inflammation-associated gastric carcinogenesis.
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