Interactions of quercetin with receptor tyrosine kinases associated with human lung carcinoma

Nat Prod Res. 2018 Dec;32(24):2928-2931. doi: 10.1080/14786419.2017.1385015. Epub 2017 Oct 12.

Abstract

Lung cancer is a deadly form of cancer with high morbidity and mortality rates. Deregulated receptor tyrosine kinases (RTKs) are frequently associated with the formation and development of lung carcinoma. Quercetin is a major dietary flavonoid that has been shown to induce cell growth inhibition and apoptosis in human lung cancer cell lines. In the current study, four major overexpressed RTKs - EGFR, FGFR1, IGF1R and c-Met - involved in human lung cancer were investigated. Molecular docking was employed to identify the binding orientation and inhibitory potential of quercetin in these RTKs. Quercetin bound to the ATP binding pocket of these kinases exhibited good binding scores and interactions by establishing hydrogen, hydrophobic and π-π interactions with the hinge region and the DFG motif in the activation loop. Thus, quercetin could be further explored as a platform for developing specific or polypharmacological compounds targeting overexpressed RTKs in lung cancer.

Keywords: Quercetin; lung cancer; molecular docking; receptor tyrosine kinases.

MeSH terms

  • Apoptosis / drug effects
  • Databases, Protein
  • ErbB Receptors / chemistry
  • ErbB Receptors / metabolism
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / enzymology
  • Lung Neoplasms / pathology
  • Molecular Docking Simulation / methods*
  • Proto-Oncogene Proteins c-met / chemistry
  • Proto-Oncogene Proteins c-met / metabolism
  • Quercetin / chemistry
  • Quercetin / metabolism
  • Quercetin / pharmacology*
  • Receptor, Fibroblast Growth Factor, Type 1 / chemistry
  • Receptor, Fibroblast Growth Factor, Type 1 / metabolism
  • Receptor, IGF Type 1
  • Receptors, Somatomedin / chemistry
  • Receptors, Somatomedin / metabolism

Substances

  • IGF1R protein, human
  • Receptors, Somatomedin
  • Quercetin
  • EGFR protein, human
  • ErbB Receptors
  • FGFR1 protein, human
  • MET protein, human
  • Proto-Oncogene Proteins c-met
  • Receptor, Fibroblast Growth Factor, Type 1
  • Receptor, IGF Type 1