1. Academic Validation
  2. Indacaterol inhibits tumor cell invasiveness and MMP-9 expression by suppressing IKK/NF-κB activation

Indacaterol inhibits tumor cell invasiveness and MMP-9 expression by suppressing IKK/NF-κB activation

  • Mol Cells. 2014 Aug;37(8):585-91. doi: 10.14348/molcells.2014.0076.
Su Ui Lee 1 Kyung-Seop Ahn 1 Min Hee Sung 1 Ji-Won Park 1 Hyung Won Ryu 1 Hyun-Jun Lee 2 Sung-Tae Hong 3 Sei-Ryang Oh 1
Affiliations

Affiliations

  • 1 Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungbuk 363-883, Korea.
  • 2 Targeted Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungbuk 363-883, Korea.
  • 3 Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.
Abstract

The β2 Adrenergic Receptor (ADRB2) is a G protein-coupled transmembrane receptor expressed in the human respiratory tract and widely recognized as a pharmacological target for treatments of asthma and chronic obstructive pulmonary disorder (COPD). Although a number of ADRB2 agonists have been developed for use in asthma therapy, indacaterol is the only ultra-long-acting inhaled β2-agonist (LABA) approved by the FDA for relieving the symptoms in COPD patients. The precise molecular mechanism underlying the pharmacological effect of indacaterol, however, remains unclear. Here, we show that β-arrestin-2 mediates the internalization of ADRB2 following indacaterol treatment. Moreover, we demonstrate that indacaterol significantly inhibits tumor necrosis factor-α (TNF-α)-induced NF-κB activity by reducing levels of both phosphorylated-IKK and -IκBα, thereby decreasing NF-κB nuclear translocation and the expression of MMP-9, an NF-κB target gene. Subsequently, we show that indacaterol significantly inhibits TNF-α/NF-κB-induced cell invasiveness and migration in a human Cancer cell line. In conclusion, we propose that indacaterol may inhibit NF-κB activity in a β-arrestin2-dependent manner, preventing further lung damage and improving lung function in COPD patients.

Keywords

ADRB2; MMP-9; NF-κB; indacaterol; invasion.

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