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

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.

• 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)

Chemical References

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

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