Abstract B68: Curcumin-induced expression of 15-hydroxyprostaglandin dehydrogenase in normal gastric mucosa RGM-1 cells: Possible involvement of AP-1

Abstract

Abstract Overproduction of prostaglandin E2 (PGE2) has been reported to be implicated in carcinogenesis. The intracellular level of PGE2 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 first step in the inactivation of PGE2. In the present study, we have found that curcumin, a yellow colouring agent present in the rhizome of Curcuma longa Linn (Zingiberaceae), induced expression of 15-PGDH in normal rat gastric mucosa cells (RGM-1) in a concentration and time dependent manner. The mRNA level of 15-PGDH was also increased by curcumin treatment. By using deletion constructs of 15-PGDH promoter, we found that activator protein-1 (AP-1) is the most essential transcription factor responsible for curcumin-induced upregulation of 15-PGDH expression. Curcumin induced phosphorylation of ERK1/2 and JNK1/2, but did not affect activation of p38 MAP kinase. However, treatment with U0126 and SP600125, pharmacological inhibitors of ERK and JNK, respectively failed to suppress the induction of 15-PGDH expression in curcumin-treated RGM-1 cells. Curcumin enhanced the expression of c-Jun, c-fos and CREB in the nuclear fraction of RGM-1 cells. In contrast, tetrahydrocurcumin which lacks the α,β-unsaturated carbonyl group failed to induce expression 15-PGDH, suggesting that the electrophilic α,β-unsaturated carbonyl group of curcumin plays a critical role in its induction of 15-PGDH expression in RGM-1 cells. These results suggest that curcumin-induced expression of 15-PGDH may be mediated by activation of AP-1 transcription factor. Citation Information: Cancer Prev Res 2011;4(10 Suppl):B68.