Rottlerin enhances IL-1beta-induced COX-2 expression through sustained p38 MAPK activation in MDA-MB-231 human breast cancer cells
Experimental & Molecular Medicine
;
: 669-675, 2011.
Artigo
em Inglês
| WPRIM
| ID: wpr-73119
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.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Acetofenonas
/
Benzopiranos
/
Neoplasias da Mama
/
Regulação Neoplásica da Expressão Gênica
/
NF-kappa B
/
Espécies Reativas de Oxigênio
/
Sistema de Sinalização das MAP Quinases
/
Mallotus (Planta)
/
Linhagem Celular Tumoral
/
Proteínas Quinases p38 Ativadas por Mitógeno
Limite:
Feminino
/
Humanos
Idioma:
Inglês
Revista:
Experimental & Molecular Medicine
Ano de publicação:
2011
Tipo de documento:
Artigo
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