title: Viscum album-mediated COX-2 inhibition implicates destabilization of COX-2 mRNA.
abstract: Extensive use of Viscum album (VA) preparations in the complementary therapy of cancer and in several other human pathologies has led to an increasing number of cellular and molecular approaches to explore the mechanisms of action of VA. We have recently demonstrated that, VA preparations exert a potent anti-inflammatory effect by selectively down-regulating the COX-2-mediated cytokine-induced secretion of prostaglandin E2 (PGE2), one of the important molecular signatures of inflammatory reactions. In this study, we observed a significant down-regulation of COX-2 protein expression in VA-treated A549 cells however COX-2 mRNA levels were unaltered. Therefore, we hypothesized that VA induces destabilisation of COX-2 mRNA, thereby depleting the available functional COX-2 mRNA for the protein synthesis and for the subsequent secretion of PGE2. To address this question, we analyzed the molecular degradation of COX-2 protein and its corresponding mRNA in A549 cell line. Using cyclohexamide pulse chase experiment, we demonstrate that, COX-2 protein degradation is not affected by the treatment with VA whereas experiments on transcriptional blockade with actinomycin D, revealed a marked reduction in the half life of COX-2 mRNA due to its rapid degradation in the cells treated with VA compared to that in IL-1β-stimulated cells. These results thus demonstrate that VA-mediated inhibition of PGE2 implicates destabilization of COX-2 mRNA.
authors: Institut National de la Santé et de la Recherche Médicale, Unité 1138, Paris, France; Université de Technologie de Compiègne, UMR CNRS 6022, Compiègne, France; Centre de Recherche des Cordeliers, Equipe-Immunopathology and therapeutic immunointervention, Paris, France.
authors: Chaitrali
authors: C
authors: Saha
authors: Institut National de la Santé et de la Recherche Médicale, Unité 1138, Paris, France; Université de Technologie de Compiègne, UMR CNRS 6022, Compiègne, France; Centre de Recherche des Cordeliers, Equipe-Immunopathology and therapeutic immunointervention, Paris, France.
authors: Pushpa
authors: P
authors: Hegde
authors: Université de Technologie de Compiègne, UMR CNRS 6022, Compiègne, France.
authors: Alain
authors: A
authors: Friboulet
authors: Institut National de la Santé et de la Recherche Médicale, Unité 1138, Paris, France; Centre de Recherche des Cordeliers, Equipe-Immunopathology and therapeutic immunointervention, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1138, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, UMR_S 1138, Paris, France.
authors: Jagadeesh
authors: J
authors: Bayry
authors: Institut National de la Santé et de la Recherche Médicale, Unité 1138, Paris, France; Centre de Recherche des Cordeliers, Equipe-Immunopathology and therapeutic immunointervention, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1138, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, UMR_S 1138, Paris, France.
authors: Srinivas V
authors: SV
authors: Kaveri
mesh_terms: D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000235:genetics*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D015536:Down-Regulation; D006801:Humans; D028321:Plant Preparations / Q000494:pharmacology; D020871:RNA Stability / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism*; D028182:Viscum album
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D028321:Plant Preparations; D012333:RNA, Messenger; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human