Myricetin suppresses p21-activated kinase 1 in human breast cancer MCF-7 cells through downstream signaling of the β-catenin pathway

Oncol Rep. 2016 Jul;36(1):342-8. doi: 10.3892/or.2016.4777. Epub 2016 Apr 28.


As a main active compound in the bark of waxberry (Myrica rubra), myricetin is a macrocyclic diarylheptanoid, and can trigger the apoptosis of HeLa and PC3 cells. The aim of the present study was to elucidate the anticancer effect of myricetin on human breast cancer MCF-7 cells and to explore the possible mechanisms of action. MCF-7 cells were treated with different concentrations of myricetin (0-80 µM) for 12, 24 and 48 h. In the present study, we found that myricetin suppressed the cell viability of the MCF-7 cells at least partly through the induction of apoptosis as determined by MTT assay and flow cytometry. Western blot analysis revealed that myricetin effectively suppressed the protein expression of p21-activated kinase 1 (PAK1), MEK and phosphorylated extracellular mitogen-activated protein kinase (ERK1/2). In addition, treatment of myricetin activated glycogen synthase kinase-3β (GSK3β) and Bax protein expression, and inhibited β-catenin/cyclin D1/proliferating cell nuclear antigen (PCNA)/survivin and promoted caspase-3 activity in the MCF-7 cells. These results demonstrated that myricetin suppressed the cell viability of human breast cancer MCF-7 cells through PAK1/MEK/ERK/GSK3β/β-catenin/cyclin D1/PCNA/survivin/Bax-caspase-3 signaling.

MeSH terms

  • Apoptosis / drug effects
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism*
  • Caspase 3 / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cyclin D1 / metabolism
  • Female
  • Flavonoids / pharmacology*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Glycogen Synthase Kinase 3 / metabolism
  • Humans
  • Inhibitor of Apoptosis Proteins / metabolism
  • MAP Kinase Signaling System / drug effects
  • MCF-7 Cells
  • Mitogen-Activated Protein Kinases / metabolism
  • Proliferating Cell Nuclear Antigen / metabolism
  • Signal Transduction / drug effects*
  • Survivin
  • bcl-2-Associated X Protein / metabolism
  • beta Catenin / metabolism*
  • p21-Activated Kinases / metabolism*


  • BIRC5 protein, human
  • Flavonoids
  • Inhibitor of Apoptosis Proteins
  • Proliferating Cell Nuclear Antigen
  • Survivin
  • bcl-2-Associated X Protein
  • beta Catenin
  • Cyclin D1
  • myricetin
  • PAK1 protein, human
  • p21-Activated Kinases
  • Mitogen-Activated Protein Kinases
  • Glycogen Synthase Kinase 3
  • Caspase 3