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3,6-dihydroxyflavone suppresses the epithelial-mesenchymal transition in breast cancer cells by inhibiting the Notch signaling pathway.
- Source :
-
Scientific reports [Sci Rep] 2016 Jun 27; Vol. 6, pp. 28858. Date of Electronic Publication: 2016 Jun 27. - Publication Year :
- 2016
-
Abstract
- The epithelial to mesenchymal transition (EMT) is a critical developmental program in cancer stem cell (CSC) maintenance and in cancer metastasis. Here, our study found that 3,6-DHF could effectively inhibit EMT in BC cells in vitro and in vivo. 3,6-DHF effectively inhibits the formation and proliferation of BCSCs, and consequently reduces the tumor-initiating capacity of tumor cells in NOD/SCID mice. Optical in vivo imaging of cancer metastasis showed that 3,6-DHF administration suppresses the lung metastasis of BC cells in vivo. Further studies indicated that 3,6-DHF down-regulates Notch1, NICD, Hes-1 and c-Myc, consequently decreasing the formation of the functional transcriptional unit of NICD-CSL-MAML, causing Notch signaling inactivation in BC cells. Over-expression of Notch1 or inhibition of miR-34a significantly reduced the inhibitory effects of 3,6-DHF on EMT, CSCs, as well as cells migration and invasion in BC cells. These data indicated that 3,6-DHF effectively inhibits EMT and CSCs, as well as cells migration and invasion in BC cells, in which miR-34a-mediated Notch1 down-regulation plays a crucial role.
- Subjects :
- Animals
Cell Line, Tumor
Cell Movement
Down-Regulation
Female
Gene Expression Regulation, Neoplastic
Humans
Lung Neoplasms drug therapy
Lung Neoplasms pathology
Lung Neoplasms secondary
MCF-7 Cells
Mammary Neoplasms, Animal drug therapy
Mammary Neoplasms, Animal metabolism
Mice
Mice, Inbred BALB C
Mice, Inbred NOD
Mice, Nude
Mice, SCID
MicroRNAs metabolism
Neoplasm Invasiveness
Neoplasm Metastasis
Neoplasm Transplantation
Neoplastic Stem Cells cytology
Receptor, Notch1 metabolism
Wound Healing
Breast Neoplasms drug therapy
Breast Neoplasms metabolism
Epithelial-Mesenchymal Transition
Flavonoids pharmacology
Receptors, Notch metabolism
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 6
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 27345219
- Full Text :
- https://doi.org/10.1038/srep28858