Induction of apoptosis by morusin in human non-small cell lung cancer cells by suppression of EGFR/STAT3 activation

Biochem Biophys Res Commun. 2018 Oct 20;505(1):194-200. doi: 10.1016/j.bbrc.2018.09.085. Epub 2018 Sep 19.


This study was designed to validate the anticancer effects of morusin in human non-small cell lung cancer (NSCLC) cells. Morusin suppressed the cell growth and colony formation in a concentration-dependent manner in H1299, H460 and H292 cells. These anticancer activities were related with apoptosis induction proved by the accumulation of chromatin condensation, PARP cleavage, increase of sub-G1 phage and annexin V-positive cell population. Interestingly, signal transducer and activator of transcription 3 (STAT3) was dephosphorylated by morusin. Morusin suppressed the transcriptional activity of STAT3 and down-regulated the expression of STAT3 target genes. In addition, morusin inhibited the phosphorylation of epithelial growth factor receptor (EGFR), an upstream regulator of STAT3. The docking study showed that morusin directly binds to the tyrosine kinase domain of EGFR. Furthermore, the anticancer effects of morusin were consistently observed in erlotinib-resistant H1975 cells expressing L858R and T790 M mutant EGFR, suggesting that morusin can be used for the advanced NSCLC with acquired resistance to EGFR TKI. Taken together, our results demonstrate that morusin induced apoptosis in human NSCLC cells regardless of EGFR mutation status through inhibition of EGFR/STAT3 activation.

Keywords: Apoptosis; EGFR; Morusin; Non-small cell lung cancer; STAT3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Drug Resistance, Neoplasm / drug effects
  • Drug Resistance, Neoplasm / genetics
  • ErbB Receptors / chemistry
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism
  • Erlotinib Hydrochloride / pharmacology
  • Flavonoids / chemistry
  • Flavonoids / metabolism
  • Flavonoids / pharmacology*
  • Humans
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Molecular Docking Simulation
  • Mutation
  • Phosphorylation / drug effects
  • Protein Binding
  • Protein Kinase Inhibitors / pharmacology
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / metabolism*


  • Flavonoids
  • Protein Kinase Inhibitors
  • STAT3 Transcription Factor
  • morusin
  • Erlotinib Hydrochloride
  • EGFR protein, human
  • ErbB Receptors