title: Rottlerin enhances IL-1β-induced COX-2 expression through sustained p38 MAPK activation in MDA-MB-231 human breast cancer cells.
abstract: Cyclooxygenase-2 (COX-2) is an important enzyme in inflammation. In this study, we investigated the underlying molecular mechanism of the synergistic effect of rottlerin on interleukin1β (IL-1β)-induced COX-2 expression in MDA-MB-231 human breast cancer cell line. Treatment with rottlerin enhanced IL-1β-induced COX-2 expression at both the protein and mRNA levels. Combined treatment with rottlerin and IL-1β significantly induced COX-2 expression, at least in part, through the enhancement of COX-2 mRNA stability. In addition, rottlerin and IL-1β treatment drove sustained activation of p38 Mitogen-activated protein kinase (MAPK), which is involved in induced COX-2 expression. Also, a pharmacological inhibitor of p38 MAPK (SB 203580) and transient transfection with inactive p38 MAPK inhibited rottlerin and IL-1β-induced COX-2 upregulation. However, suppression of protein kinase C δ (PKC δ) expression by siRNA or overexpression of dominant-negative PKC δ (DN-PKC-δ) did not abrogate the rottlerin plus IL-1β-induced COX-2 expression. Furthermore, rottlerin also enhanced tumor necrosis factor-α (TNF-α), phorbol myristate acetate (PMA), and lipopolysaccharide (LPS)-induced COX-2 expression. Taken together, our results suggest that rottlerin causes IL-1β-induced COX-2 upregulation through sustained p38 MAPK activation in MDA-MB-231 human breast cancer cells.
authors.affiliation: Department of Immunology Keimyung University School of Medicine Daegu 704-701, Korea.
authors.forename: Eun Jung
authors.initials: EJ
authors.lastname: Park
authors.forename: Taeg Kyu
authors.initials: TK
authors.lastname: Kwon
mesh_terms: D000098:Acetophenones / Q000494:pharmacology*; D001578:Benzopyrans / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000235:genetics*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D053583:Interleukin-1beta / Q000276:immunology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D036461:Mallotus Plant / Q000737:chemistry; D016328:NF-kappa B / Q000276:immunology; D051745:Protein Kinase C-delta / Q000037:antagonists & inhibitors; D017382:Reactive Oxygen Species / Q000276:immunology; D048051:p38 Mitogen-Activated Protein Kinases / Q000276:immunology*
chemical_list: D000098:Acetophenones; D001578:Benzopyrans; D004791:Enzyme Inhibitors; D053583:Interleukin-1beta; D016328:NF-kappa B; D017382:Reactive Oxygen Species; C085746:rottlerin; D051546:Cyclooxygenase 2; D051745:Protein Kinase C-delta; D048051:p38 Mitogen-Activated Protein Kinases