The Natural Alkaloid Piperlongumine Inhibits Metastatic Activity and Epithelial-to-Mesenchymal Transition of Triple-Negative Mammary Carcinoma Cells.

In this study, we determined the effect of low dose piperlongumine on the motility/invasive capacity and epithelial-to-mesenchymal transition (EMT) of MDA-MB-231 triple-negative breast cancer (TNBC) cells and the metastasis of 4T1 mouse mammary carcinoma cells. MTT assays measured the effect of pipe...

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Publicado en:Nutrition & Cancer Vol. 73; no. 11/12; pp. 2397 - 2411
Autores principales: Delaney, Leanne M., Farias, Nathan, Ghassemi Rad, Javad, Fernando, Wasundara, Annan, Henry, Hoskin, David W.
Formato: pictorial research tables/charts Journal Article
Publicado: Taylor & Francis Ltd 2021
Acceso en línea:Ver este registro en EBSCOhost
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      dt: 2021
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      pub: Taylor & Francis Ltd
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        10.1080/01635581.2020.1825755
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        atl: The Natural Alkaloid Piperlongumine Inhibits Metastatic Activity and Epithelial-to-Mesenchymal Transition of Triple-Negative Mammary Carcinoma Cells.
      aug:
        au:
          Delaney, Leanne M.
          Farias, Nathan
          Ghassemi Rad, Javad
          Fernando, Wasundara
          Annan, Henry
          Hoskin, David W.
        affil: Department of Microbiology and Immunology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada
      sug:
        subj:
          Breast Neoplasms Drug Therapy
          Neoplasm Metastasis Prevention and Control
          Plant Extracts Pharmacodynamics
          Epithelial-Mesenchymal Transition Drug Effects
          Cell Line, Tumor Drug Effects
          Alkaloids Pharmacodynamics
          Animal Studies
          Mice
          Plant Extracts Administration and Dosage
          Cell Movement Drug Effects
          Biological Assay
          Blotting, Western
          Matrix Metalloproteinases Drug Effects
          Interleukins Drug Effects
          Enzyme-Linked Immunosorbent Assay
          Gene Expression
          Polymerase Chain Reaction
          Reactive Oxygen Species
          Flow Cytometry
          Growth Substances Drug Effects
      ab: In this study, we determined the effect of low dose piperlongumine on the motility/invasive capacity and epithelial-to-mesenchymal transition (EMT) of MDA-MB-231 triple-negative breast cancer (TNBC) cells and the metastasis of 4T1 mouse mammary carcinoma cells. MTT assays measured the effect of piperlongumine on TNBC cell growth. Motility/invasiveness were determined by gap closure/transwell assays. Western blotting assessed ZEB1, Slug, and matrix metalloproteinase (MMP) 9 expression. Interleukin (IL) 6 was detected by ELISA. MMP2, E-cadherin, and miR-200c expression was determined by real-time quantitative polymerase chain reaction. Reactive oxygen species (ROS) were measured by flow cytometry. The orthotopic 4T1 mouse model of breast cancer was used to examine metastasis. Piperlongumine-treated MDA-MB-231 cells showed reduced motility/invasiveness, decreased MMP2 and MMP9 expression, increased miR-200c expression, reduced IL-6 synthesis, decreased expression of ZEB1 and Slug, increased E-cadherin expression, and epithelial-like morphology. Piperlongumine also inhibited transforming growth factor β-induced ZEB1 and Slug expression. ROS accumulated in piperlongumine-treated cells, while changes in metastasis-associated gene expression were ablated by exogenous glutathione. Metastasis of 4T1 cells to the lungs of BALB/c mice was dramatically reduced in piperlongumine-treated animals. These findings reveal a previously unknown capacity of low dose piperlongumine to interfere with TNBC metastasis via an oxidative stress-dependent mechanism.
      pubtype: Academic Journal
      doctype:
        pictorial
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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