Rhinacanthin-C Extracted from Rhinacanthus nasutus (L.) Inhibits Cholangiocarcinoma Cell Migration and Invasion by Decreasing MMP-2, uPA, FAK and MAPK Pathways

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  • Additional Information
    • Source:
      Publisher: Asian Pacific Organization for Cancer Prevention Country of Publication: Thailand NLM ID: 101130625 Publication Model: Electronic Cited Medium: Internet ISSN: 2476-762X (Electronic) Linking ISSN: 15137368 NLM ISO Abbreviation: Asian Pac J Cancer Prev Subsets: MEDLINE
    • Publication Information:
      Original Publication: Bangkok : Asian Pacific Organization for Cancer Prevention,
    • Subject Terms:
      Cell Movement/*drug effects ; Cholangiocarcinoma/*drug therapy ; Focal Adhesion Kinase 1/*metabolism ; Matrix Metalloproteinase 2/*metabolism ; Mitogen-Activated Protein Kinases/*metabolism ; Naphthoquinones/*pharmacology ; Urokinase-Type Plasminogen Activator/*metabolism; Acanthaceae/chemistry ; Animals ; Antineoplastic Agents/pharmacology ; Cell Line ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Chlorocebus aethiops ; Cholangiocarcinoma/metabolism ; Humans ; MAP Kinase Signaling System/drug effects ; NF-kappa B/metabolism ; Neoplasm Invasiveness/pathology ; Plant Extracts/pharmacology ; Signal Transduction/drug effects ; Vero Cells
    • Abstract:
      Cholangiocarcinoma is a malignant tumor with high metastatic and mortality rates. We investigated the effects of rhinacanthin-C on cell proliferation, migration, invasion and the expression of proteins regulating cancer cell invasion-regulated proteins in a cholangiocarcinoma (KKU-M156) cell line. Cytotoxicity of rhinacanthin-C was determined by the SRB assay. Using wound-migration, chamber-migration and chamber-invasion assays, we assessed the effects of rhinacanthin-C against KKU-M156 cells. The activities of matrix metalloproteinases 2 and 9 (MMP-2, MMP-9) and urokinase-type plasminogen activator (uPA) were determined using gelatinase and uPA zymography assays. The expression of invasion-regulated proteins was investigated using western-blot analysis. After treatment with rhinacanthin-C, KKU-M156 cells exhibited antiproliferative effects in a dose-dependent manner with greater efficacy than in Vero cells: IC50 values were 1.50 and 2.37 μM, respectively. Rhinacanthin-C significantly inhibited cell migration and invasion of KKU-M156 cells in a dose-dependent manner. Consistent with this observation, treatment with rhinacanthin-C was associated with a decrease in the expression levels of FAK, p-FAK, MMP-2, and a decrease in the levels of p38-, JNK1/2- and ERK1/2-MAPK pathways as well as inhibiting NF-κB/p65 expression and translocation of NF-κB/p65 to the nucleus. We have shown for the first time that the anti-metastatic effects of rhinacanthin-C on KKU-M156 cells are mediated via inhibition of the expression of invasion-regulated proteins. Rhinacanthin-C may deserve consideration as a potential agent for the treatment of cholangiocarcinoma.
      (Creative Commons Attribution License)
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    • Contributed Indexing:
      Keywords: Rhinacanthin-C*; invasion*; migration*; metastasis*
    • Accession Number:
      0 (Antineoplastic Agents)
      0 (NF-kappa B)
      0 (Naphthoquinones)
      0 (Plant Extracts)
      0 (rhinacanthin-C)
      EC 2.7.10.2 (Focal Adhesion Kinase 1)
      EC 2.7.10.2 (PTK2 protein, human)
      EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
      EC 3.4.21.73 (Urokinase-Type Plasminogen Activator)
      EC 3.4.24.24 (Matrix Metalloproteinase 2)
    • Publication Date:
      Date Created: 20181226 Date Completed: 20190408 Latest Revision: 20200225
    • Publication Date:
      20240829
    • Accession Number:
      PMC6428551
    • Accession Number:
      10.31557/APJCP.2018.19.12.3605
    • Accession Number:
      30583689