title: Pterostilbene inhibits triple-negative breast cancer metastasis via inducing microRNA-205 expression and negatively modulates epithelial-to-mesenchymal transition.
abstract: Breast cancer is the leading cause of cancer-related deaths among females in economically developing countries. Greater than 95% of breast malignancies are of epithelial origin; the induction of epithelial-to-mesenchymal transition (EMT) has been shown to initiate the metastatic process in breast carcinoma and remains the key target for drug development. Here, we examine the anti-metastatic potential of pterostilbene in modulating EMT process in breast cancer cells both in vitro and in vivo. The differential invasive ability among MCF7, Hs578t and MDA-MB-231 breast cancer cell lines were closely correlated with the expression of EMT markers, determined by Western blots and Matrigel-coated transwells assay. Pterostilbene inhibited the migratory and invasive potential of triple-negative MDA-MB-231 and Hs578t cells, accompanied by the up-regulation of E-cadherin and down-regulation of Snail, Slug, vimentin and ZEB1. Mechanistic investigations revealed a significant up-regulation of miR-205, which resulted in the reduction of Src expression in pterostilbene-treated breast cancer cells. Importantly, pterostilbene suppressed tumor growth and metastasis in MDA-MB-231-bearing NOD/SCID mice by reducing Src/Fak signaling; this observation was consistent with the negative correlations between miR-205 and Src expression in both normal and malignant breast tissues. Our findings provide supports for the usage of pterostilbene as an inhibitor of EMT process and potential candidate for adjuvant therapy.
authors: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan; Department of Surgery, Taipei Medical University Shuang Ho Hospital, Taipei 235, Taiwan.
authors: Chih-Ming
authors: CM
authors: Su
authors: Department of Pathology, Taipei Medical University Shuang Ho Hospital, Taipei 235, Taiwan.
authors: Wei-Hwa
authors: WH
authors: Lee
authors: College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan; Translational Research Laboratory, Cancer Center, Taipei Medical University Hospital, Taipei 110, Taiwan.
authors: Alexander T H
authors: AT
authors: Wu
authors: Biostatistics and Research Consultation Center, Taipei Medical University, Taipei 110, Taiwan.
authors: Yen-Kuang
authors: YK
authors: Lin
authors: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan; Division of Thoracic Surgery, Department of Surgery, Taipei Medical University Shuang Ho Hospital, Taipei 235, Taiwan.
authors: Liang-Shun
authors: LS
authors: Wang
authors: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan; Department of Surgery, Taipei Medical University Shuang Ho Hospital, Taipei 235, Taiwan. Electronic address: chwu@tmu.edu.tw.
authors: Chih-Hsiung
authors: CH
authors: Wu
authors: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan; Department of Medical Research and Education, Taipei Medical University Shuang Ho Hospital, Taipei 235, Taiwan. Electronic address: ctyeh@s.tmu.edu.tw.
authors: Chi-Tai
authors: CT
authors: Yeh
mesh_terms: D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005260:Female; D051417:Focal Adhesion Kinase 1 / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013267:Stilbenes / Q000494:pharmacology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D064726:Triple Negative Breast Neoplasms / Q000235:genetics*; D015854:Up-Regulation; D014746:Vimentin / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D000071799:Zinc Finger E-box-Binding Homeobox 1; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D015820:Cadherins; D051417:Focal Adhesion Kinase 1; D018398:Homeodomain Proteins; D035683:MicroRNAs; D051057:Proto-Oncogene Proteins c-akt; D034741:RNA, Small Interfering; D013267:Stilbenes; D014157:Transcription Factors; D014746:Vimentin; D000071799:Zinc Finger E-box-Binding Homeobox 1; D019061:src-Family Kinases; C534425:MIR205, human; C486307:ZEB1 protein, human; C107773:pterostilbene; C496050:PTK2 protein, human
keywords: Epithelial-to-mesenchymal transition (EMT); Metastasis; Pterostilbene; Triple-negative breast cancer; miR-205