Magnolol down-regulates HER2 gene expression, leading to inhibition of HER2-mediated metastatic potential in ovarian cancer cells

Cancer Lett. 2011 Dec 1;311(1):11-9. doi: 10.1016/j.canlet.2011.06.007. Epub 2011 Jun 25.


Overexpression of the HER2 oncogene contributes to tumor cell invasion, metastasis and angiogenesis and correlates with poor prognosis. Magnolol has been reported to exhibit anti-tumor activities. However, the molecular mechanism of action of magnolol has not been investigated in HER2-positive cancer cells. Therefore, we examined the anti-cancer effects of magnolol on HER2-overexpressing ovarian cancer cells. Magnolol treatment caused a dose-dependent inhibition of HER2 gene expression at the transcriptional level, potentially in part through suppression of NF-κB activation. Treatment of HER2-overexpressing ovarian cancer cells with magnolol down-regulated the HER2 downstream PI3K/Akt signaling pathway, and suppressed the expression of downstream target genes, vascular endothelial growth factor (VEGF), matrix metalloproteinase 2 (MMP2) and cyclin D1. Consistently, magnolol-mediated inhibition of MMP2 activity could be prevented by co-treatment with epidermal growth factor. Migration assays revealed that magnolol treatment markedly reduced the motility of HER2-overexpressing ovarian cancer cells. Furthermore, magnolol-induced apoptosis in HER2-overexpressing ovarian cancer cells was characterized by the up-regulation of cleaved poly(ADP-ribose) polymerase (PARP) and activated caspase 3. These findings suggest that magnolol may act against HER2 and its downstream PI3K/Akt/mTOR-signaling network, thus resulting in suppression of HER2-mediated transformation and metastatic potential in HER2-overexpressing ovarian cancers. These results provide a novel mechanism to explain the anti-cancer effect of magnolol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biphenyl Compounds / pharmacology*
  • Caspase 3 / metabolism
  • Cell Growth Processes / drug effects
  • Cell Growth Processes / genetics
  • Cell Line, Tumor
  • Cell Transformation, Neoplastic / drug effects
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism
  • Cyclin D1 / biosynthesis
  • Cyclin D1 / genetics
  • Down-Regulation / drug effects
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Genes, erbB-2 / drug effects
  • Humans
  • Lignans / pharmacology*
  • Neoplasm Metastasis
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / enzymology
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / pathology
  • Phosphatidylinositol 3-Kinases / metabolism
  • Poly(ADP-ribose) Polymerases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Receptor, ErbB-2 / antagonists & inhibitors
  • Receptor, ErbB-2 / biosynthesis
  • Receptor, ErbB-2 / genetics*
  • Signal Transduction / drug effects
  • TOR Serine-Threonine Kinases / metabolism
  • Vascular Endothelial Growth Factor A / biosynthesis
  • Vascular Endothelial Growth Factor A / genetics


  • Biphenyl Compounds
  • CCND1 protein, human
  • Lignans
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • magnolol
  • Cyclin D1
  • Poly(ADP-ribose) Polymerases
  • MTOR protein, human
  • Receptor, ErbB-2
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • Caspase 3