Rottlerin enhances IL-1beta-induced COX-2 expression through sustained p38 MAPK activation in MDA-MB-231 human breast cancer cells.
10.3858/emm.2011.43.12.077
- Author:
Eun Jung PARK
1
;
Taeg Kyu KWON
Author Information
1. Department of Immunology, Keimyung University School of Medicine, Daegu 704-701, Korea. kwontk@dsmc.or.kr
- Publication Type:Original Article
- Keywords:
breast neoplasms;
cyclooxygenase-2;
interleukin-1beta;
p38 mitogen-activated protein kinases;
RNA stability;
rottlerin
- MeSH:
Acetophenones/*pharmacology;
Benzopyrans/*pharmacology;
Breast Neoplasms/drug therapy/*genetics/immunology;
Cell Line, Tumor;
Cyclooxygenase 2/*genetics;
Enzyme Activation/drug effects;
Enzyme Inhibitors/*pharmacology;
Female;
Gene Expression Regulation, Neoplastic/*drug effects;
Humans;
Interleukin-1beta/*immunology;
MAP Kinase Signaling System/drug effects;
Mallotus Plant/chemistry;
NF-kappa B/immunology;
Protein Kinase C-delta/antagonists & inhibitors;
Reactive Oxygen Species/immunology;
p38 Mitogen-Activated Protein Kinases/*immunology
- From:Experimental & Molecular Medicine
2011;43(12):669-675
- CountryRepublic of Korea
- Language:English
-
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 interleukin1beta (IL-1beta)-induced COX-2 expression in MDA-MB-231 human breast cancer cell line. Treatment with rottlerin enhanced IL-1beta-induced COX-2 expression at both the protein and mRNA levels. Combined treatment with rottlerin and IL-1beta significantly induced COX-2 expression, at least in part, through the enhancement of COX-2 mRNA stability. In addition, rottlerin and IL-1beta 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-1beta-induced COX-2 upregulation. However, suppression of protein kinase C delta (PKC delta) expression by siRNA or overexpression of dominant-negative PKC delta (DN-PKC-delta) did not abrogate the rottlerin plus IL-1beta-induced COX-2 expression. Furthermore, rottlerin also enhanced tumor necrosis factor-alpha (TNF-alpha), phorbol myristate acetate (PMA), and lipopolysaccharide (LPS)-induced COX-2 expression. Taken together, our results suggest that rottlerin causes IL-1beta-induced COX-2 upregulation through sustained p38 MAPK activation in MDA-MB-231 human breast cancer cells.
