Sodium Phenylbutyrate Inhibits Tumor Growth and the Epithelial-Mesenchymal Transition of Oral Squamous Cell Carcinoma In Vitro and In Vivo.

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  • Additional Information
    • Source:
      Publisher: Mary Ann Liebert, Inc Country of Publication: United States NLM ID: 9605408 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1557-8852 (Electronic) Linking ISSN: 10849785 NLM ISO Abbreviation: Cancer Biother Radiopharm Subsets: MEDLINE
    • Publication Information:
      Original Publication: Larchmont, NY : Mary Ann Liebert, Inc., c1996-
    • Subject Terms:
      Carcinoma, Squamous Cell/*drug therapy ; Mouth Neoplasms/*drug therapy ; Phenylbutyrates/*therapeutic use; Animals ; Apoptosis ; Carcinoma, Squamous Cell/pathology ; Cell Line, Tumor ; Cell Movement ; Epithelial-Mesenchymal Transition ; Humans ; Mice, Nude ; Mouth Neoplasms/pathology ; Phenylbutyrates/pharmacology
    • Abstract:
      Sodium phenylbutyrate (SPB) as a salt of 4-phenylbutyric acid (4-PBA) has been reported to be an ammonia scavenger, histone deacetylase inhibitor, and an endoplasmic reticulum stress inhibitor in various diseases, including neurological diseases, inflammatory disorders, and carcinogenesis. Although phenylbutyrate showed effective antitumor properties in many cancers, its role in oral squamous cell carcinoma (OSCC) remains further characterized. Thus, the OSCC cell lines CAL27, HSC3, and SCC4 were treated with a series of doses of SPB for different times. The IC 50 of three cell lines for SPB was determined to be 4.0, 3.7, and 3.0 mM. The CCK-8 assay indicated that the treatment of SPB induced continuous inhibition of cell vitality of three cell lines. Apoptosis was assessed by Hoechst assay that showed that SPB could significantly promote cell apoptosis. Moreover, the apoptosis-related pathway was analyzed, and the results showed that the expression of antiapoptosis factor BCL-2 was downregulated by SPB but the cleavage of caspase-3 was increased. Meanwhile, it was found that SPB also impaired the migration and invasion of OSCC cells in vitro. Mechanistically, the transforming growth factor-β (TGFB) related epithelial-mesenchymal transition (EMT) was inhibited by SPB with decreased mesenchymal marker N-cadherin and increased epithelial marker E-cadherin. Furthermore, the antitumor effect of SPB in vivo was also demonstrated. The administration of SPB induced remarkably tumor regression with decreased tumor volume, and the TGFB level and EMT phenotype in vivo were also inhibited. These data demonstrated that the treatment of SPB could function as antitumor therapeutics for OSCC.
    • Contributed Indexing:
      Keywords: EMT; OSCC; apoptosis; migration; sodium phenylbutyrate
    • Accession Number:
      0 (Phenylbutyrates)
      7WY7YBI87E (4-phenylbutyric acid)
    • Publication Date:
      Date Created: 20180417 Date Completed: 20180919 Latest Revision: 20180919
    • Publication Date:
      20240829
    • Accession Number:
      10.1089/cbr.2017.2418
    • Accession Number:
      29658787