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.
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.
Xiao
Jian
J
Department of Pathophysiology, Sun Yat-Sen University, Guangzhou 510080, P. R. China.
Tan
Yi
Y
Pan
Yunbao
Y
Liang
Guang
G
Qu
Changju
C
Zhang
Xie
X
Zhang
Yi
Y
Li
Xiaokun
X
Yang
Huiling
H
D020413:3' Untranslated Regions; D001483:Base Sequence; D001969:Bromobenzenes / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology; D051546:Cyclooxygenase 2 / Q000235:genetics*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D017931:DNA Primers; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D010422:Pentanones / Q000494:pharmacology*; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000235:genetics*
C550703:1,5-bis(2-bromophenyl)penta-1,4-dien-3-one; D020413:3' Untranslated Regions; D001969:Bromobenzenes; D052246:Cyclooxygenase 2 Inhibitors; D017931:DNA Primers; D010422:Pentanones; D012333:RNA, Messenger; D051546:Cyclooxygenase 2; D003474:Curcumin