3,6-Dihydroxyflavone suppresses the epithelial-mesenchymal transition in breast cancer cells by inhibiting the Notch signaling pathway.

3,6-Dihydroxyflavone(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[1].

Cells were cultured in six-well plates until they reached 100% confluence. A vertical or horizontal wound was gently created in monolayers using a 20 μl sterile pipette tip. The cells were then washed for 3 times with growth medium to remove the detached cells, and the medium was added with fresh medium treated with 3,6-DHF. Images were captured using an inverted microscope and camera at designed times to assess the inhibition of wound closure[1].