Daidzein suppresses tumor necrosis factor-α induced migration and invasion by inhibiting hedgehog/Gli1 signaling in human breast cancer cells

J Agric Food Chem. 2014 Apr 30;62(17):3759-67. doi: 10.1021/jf500231t. Epub 2014 Apr 22.


In breast cancer, the cytokine tumor necrosis factor-α (TNF-α) induces cell invasion, although the molecular basis of it has not been clearly elucidated. In this study, we investigated the role of daidzein in regulating TNF-α induced cell invasion and the underlying molecular mechanisms. Daidzein inhibited TNF-α induced cellular migration and invasion in estrogen receptor (ER) negative MCF10DCIS.com human breast cancer cells. TNF-α activated Hedgehog (Hh) signaling by enhancing Gli1 nuclear translocation and transcriptional activity, which resulted in increased invasiveness; these effects were blocked by daidzein and the Hh signaling inhibitors, cyclopamine and vismodegib. Moreover, these compounds suppressed TNF-α induced matrix metalloproteinase (MMP)-9 mRNA expression and activity. Taken together, mammary tumor cell invasiveness was stimulated by TNF-α induced activation of Hh signaling; these effects were abrogated by daidzein, which suppressed Gli1 activation, thereby inhibiting migration and invasion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Breast Neoplasms / physiopathology*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Nucleolus / genetics
  • Cell Nucleolus / metabolism
  • Down-Regulation / drug effects
  • Female
  • Hedgehogs / genetics
  • Hedgehogs / metabolism*
  • Humans
  • Isoflavones / pharmacology*
  • Neoplasm Invasiveness / genetics
  • Oncogene Proteins / genetics
  • Oncogene Proteins / metabolism*
  • Plant Extracts / pharmacology*
  • Signal Transduction / drug effects*
  • Soybeans / chemistry*
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism*
  • Zinc Finger Protein GLI1


  • Isoflavones
  • Oncogene Proteins
  • Plant Extracts
  • Trans-Activators
  • Tumor Necrosis Factor-alpha
  • Zinc Finger Protein GLI1
  • daidzein