title: 3,6-dihydroxyflavone suppresses the epithelial-mesenchymal transition in breast cancer cells by inhibiting the Notch signaling pathway.
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.
authors.affiliation: Research Center for Nutrition and Food Safety, Third Military Medical University; Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing, China.
authors.forename: Junli
authors.initials: J
authors.lastname: Chen
authors.affiliation: Research Center for Nutrition and Food Safety, Third Military Medical University; Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Chang
authors.affiliation: Research Center for Nutrition and Food Safety, Third Military Medical University; Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing, China.|Department of Public Health, School of Preclinical Medicine, Chengdu Medical College, Chengdu, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Peng
authors.affiliation: Research Center for Nutrition and Food Safety, Third Military Medical University; Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing, China.
authors.forename: Yeyun
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Research Center for Nutrition and Food Safety, Third Military Medical University; Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing, China.
authors.forename: Long
authors.initials: L
authors.lastname: Yi
authors.affiliation: Research Center for Nutrition and Food Safety, Third Military Medical University; Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing, China.
authors.forename: Qianyong
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Research Center for Nutrition and Food Safety, Third Military Medical University; Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing, China.
authors.forename: Jundong
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Research Center for Nutrition and Food Safety, Third Military Medical University; Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing, China.
authors.forename: Mantian
authors.initials: M
authors.lastname: Mi
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000556:secondary; D061986:MCF-7 Cells; D015674:Mammary Neoplasms, Animal / Q000188:drug therapy / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D008819:Mice, Nude; D016513:Mice, SCID; D035683:MicroRNAs / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000166:cytology; D051881:Receptor, Notch1 / Q000378:metabolism; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction; D014945:Wound Healing
chemical_list: C555160:3,6-dihydroxyflavone; D005419:Flavonoids; D035683:MicroRNAs; C497762:Notch1 protein, mouse; D051881:Receptor, Notch1; D051880:Receptors, Notch