Rottlerin enhances IL-1β-induced COX-2 expression through sustained p38 MAPK activation in MDA-MB-231 human breast cancer cells

Exp Mol Med. 2011 Dec 31;43(12):669-75. doi: 10.3858/emm.2011.43.12.077.


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.

MeSH terms

  • Acetophenones / pharmacology*
  • Benzopyrans / pharmacology*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / 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*


  • Acetophenones
  • Benzopyrans
  • Enzyme Inhibitors
  • Interleukin-1beta
  • NF-kappa B
  • Reactive Oxygen Species
  • rottlerin
  • Cyclooxygenase 2
  • Protein Kinase C-delta
  • p38 Mitogen-Activated Protein Kinases