Abstract |
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.
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Authors | Cheng Bao, Hyeju Namgung, Jaehoo Lee, Hyun-Chang Park, Jiwon Ko, Heejung Moon, Hyuk Wan Ko, Hong Jin Lee |
Journal | Journal of agricultural and food chemistry
(J Agric Food Chem)
Vol. 62
Issue 17
Pg. 3759-67
(Apr 30 2014)
ISSN: 1520-5118 [Electronic] United States |
PMID | 24724627
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Isoflavones
- Oncogene Proteins
- Plant Extracts
- Trans-Activators
- Tumor Necrosis Factor-alpha
- Zinc Finger Protein GLI1
- daidzein
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Topics |
- Animals
- Breast Neoplasms
(drug therapy, genetics, pathology, physiopathology)
- Cell Line, Tumor
- Cell Movement
(drug effects)
- Cell Nucleolus
(genetics, metabolism)
- Down-Regulation
(drug effects)
- Female
- Hedgehogs
(genetics, metabolism)
- Humans
- Isoflavones
(pharmacology)
- Neoplasm Invasiveness
(genetics)
- Oncogene Proteins
(genetics, metabolism)
- Plant Extracts
(pharmacology)
- Signal Transduction
(drug effects)
- Soybeans
(chemistry)
- Trans-Activators
(genetics, metabolism)
- Tumor Necrosis Factor-alpha
(genetics, metabolism)
- Zinc Finger Protein GLI1
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