Role of licochalcone A in VEGF-induced proliferation of human airway smooth muscle cells: implications for asthma

Growth Factors. 2017 Feb;35(1):39-47. doi: 10.1080/08977194.2017.1338694.

Abstract

Asthma is a chronic respiratory disease characterized by reversible airway obstruction with persistent airway inflammation and airway remodeling, which is associated with increased airway smooth muscle (ASM) mass. Licochalcone A is the predominant characteristic chalcone in licorice root. We found that licochalcone A inhibited vascular endothelial growth factor (VEGF)-induced ASM cell proliferation and induced cell cycle arrest. Additionally, VEGF-induced ASM cell proliferation was suppressed via inhibition of extracellular signal-regulated kinase 1/2 (ERK1/2) activity, but not that of Akt. Furthermore, licochalcone A treatment inhibited VEGF-induced activation of VEGF receptor 2 (VEGFR2) and ERK and blocked the downregulation of caveolin-1 in a concentration-dependent manner. Collectively, our findings suggested that licochalcone A inhibited VEGF-induced ASM cell proliferation by suppressing VEGFR2 and ERK1/2 activation and downregulating caveolin-1. Further studies of these mechanisms are needed to facilitate the development of treatments for smooth muscle hyperplasia-associated diseases of the airway, such as asthma.

Keywords: Asthma; airway smooth muscle; licochalcone A; vascular endothelial growth factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asthma / metabolism*
  • Caveolin 1 / metabolism
  • Cell Proliferation*
  • Cells, Cultured
  • Chalcones / pharmacology*
  • Humans
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Myocytes, Smooth Muscle / drug effects*
  • Myocytes, Smooth Muscle / metabolism
  • Myocytes, Smooth Muscle / physiology
  • Respiratory System / cytology*
  • Vascular Endothelial Growth Factor A / pharmacology
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism

Substances

  • Caveolin 1
  • Chalcones
  • Vascular Endothelial Growth Factor A
  • KDR protein, human
  • Vascular Endothelial Growth Factor Receptor-2
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • licochalcone A