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


ABSTRACT: The ?2 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 ?2-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 ?-arrestin-2 mediates the internalization of ADRB2 following indacaterol treatment. Moreover, we demonstrate that indacaterol significantly inhibits tumor necrosis factor-? (TNF-?)-induced NF-?B activity by reducing levels of both phosphorylated-IKK and -I?B?, thereby decreasing NF-?B nuclear translocation and the expression of MMP-9, an NF-?B target gene. Subsequently, we show that indacaterol significantly inhibits TNF-?/NF-?B-induced cell invasiveness and migration in a human cancer cell line. In conclusion, we propose that indacaterol may inhibit NF-?B activity in a ?-arrestin2-dependent manner, preventing further lung damage and improving lung function in COPD patients.

SUBMITTER: Lee SU 

PROVIDER: S-EPMC4145369 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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

Lee Su Ui SU   Ahn Kyung-Seop KS   Sung Min Hee MH   Park Ji-Won JW   Ryu Hyung Won HW   Lee Hyun-Jun HJ   Hong Sung-Tae ST   Oh Sei-Ryang SR  

Molecules and cells 20140818 8


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 unde  ...[more]

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