title: Chrysin inhibits metastatic potential of human triple-negative breast cancer cells by modulating matrix metalloproteinase-10, epithelial to mesenchymal transition, and PI3K/Akt signaling pathway.
abstract: Chrysin, a naturally occurring flavone, has been shown to inhibit cell proliferation and induce cell apoptosis in various cancers. However, the effect and mechanisms of chrysin on cancer metastasis are still enigmatic. In this study, metastatic triple-negative breast cancer (TNBC) cell lines were used to evaluate the antimetastatic activity of chrysin. The results showed that chrysin (5, 10 and 20 μM) significantly suppressed TNBC cell migration and invasion in a dose-dependent manner. Human matrix metalloproteinase (MMP) antibody array demonstrated that MMP-10 was downregulated by chrysin, which was further verified by Western blotting and ELISA. Moreover, it was shown that chrysin induced increased E-cadherin expression and decreased expression of vimentin, snail and slug in TNBC cells, suggesting that chrysin had a reversal effect on epithelial-mesenchymal transition. More importantly, it was demonstrated that inhibiting the Akt signal pathway might play a central role in chrysin-induced antimetastatic activity by regulating MMP-10 and epithelial-mesenchymal transition. In conclusion, our study indicates that chrysin exerts antimetastatic activities in TNBC cells, which suggests that chrysin might be a potential therapeutic candidate for the treatment of advanced or metastatic breast cancer.
authors.affiliation: Molecular Oncology and Epigenetics Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Yang
authors.forename: Jing
authors.initials: J
authors.lastname: Huang
authors.forename: Tingxiu
authors.initials: T
authors.lastname: Xiang
authors.forename: Xuedong
authors.initials: X
authors.lastname: Yin
authors.forename: Xinrong
authors.initials: X
authors.lastname: Luo
authors.forename: Jianbo
authors.initials: J
authors.lastname: Huang
authors.forename: Fuling
authors.initials: F
authors.lastname: Luo
authors.forename: Hongyuan
authors.initials: H
authors.lastname: Li
authors.forename: Hongzhong
authors.initials: H
authors.lastname: Li
authors.forename: Guosheng
authors.initials: G
authors.lastname: Ren
mesh_terms: D015703:Antigens, CD; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D053506:Matrix Metalloproteinase 10 / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D064726:Triple Negative Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D014746:Vimentin / Q000235:genetics / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects
chemical_list: D015703:Antigens, CD; D000970:Antineoplastic Agents; C513384:CDH1 protein, human; D015820:Cadherins; D005419:Flavonoids; D014746:Vimentin; C043561:chrysin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C511770:MMP10 protein, human; D053506:Matrix Metalloproteinase 10
keywords: breast cancer; chrysin; epithelial-mesenchymal transition; matrix metalloproteinase; phosphatidylinositol 3-kinase