Daidzein suppresses tumor necrosis factor-α induced migration and invasion by inhibiting hedgehog/Gli1 signaling in human breast cancer cells.
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.
Department of Food Science and Technology, Chung-Ang University , 4726 Seodongdaero, Anseong 456-756, South Korea.
Cheng
C
Bao
Hyeju
H
Namgung
Jaehoo
J
Lee
Hyun-Chang
HC
Park
Jiwon
J
Ko
Heejung
H
Moon
Hyuk Wan
HW
Ko
Hong Jin
HJ
Lee
D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002466:Cell Nucleolus / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D006364:Hedgehogs / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology*; D009361:Neoplasm Invasiveness / Q000235:genetics; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D010936:Plant Extracts / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D013025:Glycine max / Q000737:chemistry*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*; D000071676:Zinc Finger Protein GLI1
D007529:Isoflavones; D015513:Oncogene Proteins; D010936:Plant Extracts; D015534:Trans-Activators; D014409:Tumor Necrosis Factor-alpha; D000071676:Zinc Finger Protein GLI1; C004742:daidzein