A New Cyclooxygenase-2 Inhibitor, (1E,4E)-1,5-Bis(2-bromophenyl)penta-1,4-dien-3-one (GL63) Suppresses Cyclooxygenase-2 Gene Expression in Human Lung Epithelial Cancer Cells: Coupled mRNA Stabilization and Posttranscriptional Inhibition

Jian Xiao; Yi Tan; Yunbao Pan; Guang Liang; Changju Qu; Xie Zhang; Yi Zhang; Xiaokun Li; Huiling Yang

doi:10.1248/bpb.33.1170

Regular Articles

A New Cyclooxygenase-2 Inhibitor, (1E,4E)-1,5-Bis(2-bromophenyl)penta-1,4-dien-3-one (GL63) Suppresses Cyclooxygenase-2 Gene Expression in Human Lung Epithelial Cancer Cells: Coupled mRNA Stabilization and Posttranscriptional Inhibition

Jian Xiao, Yi Tan, Yunbao Pan, Guang Liang, Changju Qu, Xie Zhang, Yi Zhang, Xiaokun Li, Huiling Yang

Author information

Jian Xiao
Department of Pathophysiology, Sun Yat-Sen University
Key Laboratory of Biotechnology Pharmaceutical Engineering, Wenzhou Medical College, School of Pharmaceutical Science
Yi Tan
Key Laboratory of Biotechnology Pharmaceutical Engineering, Wenzhou Medical College, School of Pharmaceutical Science
Department of Pediatrics, University of Louisville
Yunbao Pan
Department of Pathophysiology, Sun Yat-Sen University
Guang Liang
Key Laboratory of Biotechnology Pharmaceutical Engineering, Wenzhou Medical College, School of Pharmaceutical Science
Changju Qu
Department of Pathophysiology, Sun Yat-Sen University
Xie Zhang
Key Laboratory of Biotechnology Pharmaceutical Engineering, Wenzhou Medical College, School of Pharmaceutical Science
Yi Zhang
Key Laboratory of Biotechnology Pharmaceutical Engineering, Wenzhou Medical College, School of Pharmaceutical Science
Xiaokun Li
Key Laboratory of Biotechnology Pharmaceutical Engineering, Wenzhou Medical College, School of Pharmaceutical Science
Huiling Yang
Department of Pathophysiology, Sun Yat-Sen University

Keywords: curcumin analogue, cyclooxygenase-2, human antigen R, posttranscription

JOURNAL FREE ACCESS

2010 Volume 33 Issue 7 Pages 1170-1175

DOI https://doi.org/10.1248/bpb.33.1170

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Abstract

Lung cancer is a leading cause of morbidity and mortality worldwide. Cyclooxygenase-2 (COX-2) expression is upregulated in lung carcinomas and is considered an attractive therapeutic target. In this study, the effect of curcumin and curcumin analogues on COX-2 expression induced by phorbol 12-myristate 13-acetate (PMA) were investigated. We found that a novel curcumin analogue (GL63) inhibited PMA-induced COX-2 mRNA and protein levels in H460 cells to a greater degree than curcumin. To understand the molecular mechanisms governing COX-2 regulation, the effect on COX-2 mRNA degradation was examined; we found that GL63 significantly decreased COX-2 mRNA stability by reducing cytoplasmic localization and protein abundance of human antigen R (HuR). The 3′-untranslated region (3′-UTR) report gene assay also showed GL63 substantially reduced the 3′-UTR green fluorescent protein values, indicating that the destabilizing effect on COX-2 mRNA may be couple with the posttranscriptional inhibition of COX-2. Taken together, our results provide evidence that the novel curcumin analogue can effectively inhibit PMA-induced COX-2 expression in H460 cells, a mechanism associated with COX-2 mRNA stability and post-transcriptional regulation.

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