title: Luteolin suppresses the metastasis of triple-negative breast cancer by reversing epithelial-to-mesenchymal transition via downregulation of β-catenin expression.
abstract: The metastasis of breast cancer is associated with dismal prognosis and high mortality due to the lack of effective treatment. Luteolin, a natural flavonoid compound, has been shown to exert antitumor activity in various types of cancers. However, the effects and mechanisms of luteolin on the metastasis of triple-negative breast cancer (TNBC) remain elusive. In the present study, we found that pretreatment of highly metastatic TNBC cell lines with luteolin dose‑dependently inhibited cell migration and invasion, and reversed epithelial-mesenchymal transition (EMT) as determined by altered morphological characteristics, downregulated epithelial markers and upregulated mesenchymal markers, and inhibited EMT-related transcription factors. In an in vivo metastasis experiment using a xenograft model, luteolin markedly inhibited lung metastases of breast cancer and the expression of EMT molecules vimentin and Slug in primary tumor tissues. Notably, luteolin also suppressed the expression of β-catenin mRNA and protein in vitro and in vivo. Furthermore, overexpression of β-catenin by adenoviruses blocked these benefits of luteolin on invasion and metastases of breast cancer. In conclusion, all these results indicated that luteolin effectively suppressed metastases of breast cancer by reversing EMT, which may be mediated by downregulation of β-catenin.
authors.affiliation: Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Dan
authors.initials: D
authors.lastname: Lin
authors.affiliation: Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Ge
authors.initials: G
authors.lastname: Kuang
authors.affiliation: Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Jingyuan
authors.initials: J
authors.lastname: Wan
authors.affiliation: Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Molecular Oncology and Epigenetics Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Hongzhong
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Anatomy, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Xia
authors.initials: X
authors.lastname: Gong
authors.affiliation: Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Hongyuan
authors.initials: H
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005260:Female; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000378:metabolism / Q000517:prevention & control* / Q000556:secondary; D047311:Luteolin / Q000494:pharmacology*; D051379:Mice; D008819:Mice, Nude; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D064726:Triple Negative Breast Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays; D051176:beta Catenin / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D051176:beta Catenin; D047311:Luteolin