title: Triptolide inhibits COX-2 expression by regulating mRNA stability in TNF-α-treated A549 cells.
abstract: Cyclooxygenase-2 (COX-2) over-expression is frequently associated with human non-small-cell lung cancer (NSCLC) and involved in tumor proliferation, invasion, angiogenesis and resistance to apoptosis. In the present study, the effects of triptolide on COX-2 expression in A549 cells were investigated and triptolide was found to inhibit TNF-α-induced COX-2 expression. In our further studies, it was found that triptolide decreased the half-life of COX-2 mRNA dramatically and that it inhibited 3'-untranslated region (3'-UTR) fluorescence reporter gene activity. Meanwhile, triptolide inhibited the HuR shuttling from nucleus to cytoplasm. After triptolide treatment, decreased COX-2 mRNA in pull-down experiments with anti-HuR antibodies was observed, indicating that the decreased cytoplasmic HuR is responsible for the decreased COX-2 mRNA. Taken together, our results provided evidence for the first time that triptolide inhibited COX-2 expression by COX-2 mRNA stability modulation and post-transcriptional regulation. These results provide a novel mechanism of action for triptolide which may be important in the treatment of lung cancer.
authors.affiliation: Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Lixin
authors.initials: L
authors.lastname: Sun
authors.forename: Shuang
authors.initials: S
authors.lastname: Zhang
authors.forename: Zhenzhou
authors.initials: Z
authors.lastname: Jiang
authors.forename: Xin
authors.initials: X
authors.lastname: Huang
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Xiao
authors.initials: X
authors.lastname: Huang
authors.forename: Han
authors.initials: H
authors.lastname: Li
authors.forename: Luyong
authors.initials: L
authors.lastname: Zhang
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D004224:Diterpenes / Q000494:pharmacology*; D051959:ELAV Proteins / Q000378:metabolism; D004852:Epoxy Compounds / Q000494:pharmacology; D006801:Humans; D010616:Phenanthrenes / Q000494:pharmacology*; D020871:RNA Stability / Q000187:drug effects*; D012333:RNA, Messenger / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D018906:Antineoplastic Agents, Alkylating; D052246:Cyclooxygenase 2 Inhibitors; D004224:Diterpenes; D051959:ELAV Proteins; D004852:Epoxy Compounds; D010616:Phenanthrenes; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C001899:triptolide; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human