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October 2013 Volume 32 Issue 4

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Article

The HDAC inhibitor, panobinostat, induces apoptosis by suppressing the expresssion of specificity protein 1 in oral squamous cell carcinoma

  • Authors:
    • Young-Joo Jeon
    • Seon Mi Ko
    • Jin Hyoung Cho
    • Jung-Il Chae
    • Jung-Hyun Shim
  • View Affiliations / Copyright

    Affiliations: Department of Oral Pharmacology, School of Dentistry and Institute of Dental Bioscience, BK21 project, Chonbuk National University, Jeonju 651-756, Republic of Korea, Department of Pharmacy, College of Pharmacy, Mokpo National University, Muan-gun, Jeonnam 534-729, Republic of Korea
  • Pages: 860-866
    |
    Published online on: July 18, 2013
       https://doi.org/10.3892/ijmm.2013.1451
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Abstract

Inhibitors of histone deacetylases (HDACs) represent a novel class of therapeutic anticancer agents. Panobinostat (LBH589) induces apoptosis through the regulation of specificity protein 1 (Sp1) in the oral squamous cell carcinoma (OSCC) cell lines, HN22 and HSC4. In this study, we analyzed the underlying signaling pathways and the mechanisms involved in this process by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay, 4',6-diamidino-2-phenylindole (DAPI) staining, immunocytochemistry and western blot analysis. LBH589 significantly reduced cell growth and the sub-G1 cell population and induced apoptosis. Sp1 protein expression was significantly reduced following treatment with LBH589 in a concentration-dependent manner. Furthermore, LBH589 upregulated the expression of p27 and p21 and downregulated the expression of cyclin D1, myeloid cell leukemia-1 (Mcl-1) and survivin; this led to the activation of apoptotic signaling pathways through the increase of Bax expression and the decrease of Bid and Bcl-xL expression. Treatment with LBH589 also induced the cleavage of caspase‑3 and PARP in the HN22 and HSC4 cells. Taken together, our data demonstrate that LBH589 induces the apoptosis of OSCC cells by suppressing Sp1 expression, indicating that LBH589 may be a promising chemotherapeutic agent for the treatment of OSCC.
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Copy and paste a formatted citation
Spandidos Publications style
Jeon Y, Ko SM, Cho JH, Chae J and Shim J: The HDAC inhibitor, panobinostat, induces apoptosis by suppressing the expresssion of specificity protein 1 in oral squamous cell carcinoma. Int J Mol Med 32: 860-866, 2013.
APA
Jeon, Y., Ko, S.M., Cho, J.H., Chae, J., & Shim, J. (2013). The HDAC inhibitor, panobinostat, induces apoptosis by suppressing the expresssion of specificity protein 1 in oral squamous cell carcinoma. International Journal of Molecular Medicine, 32, 860-866. https://doi.org/10.3892/ijmm.2013.1451
MLA
Jeon, Y., Ko, S. M., Cho, J. H., Chae, J., Shim, J."The HDAC inhibitor, panobinostat, induces apoptosis by suppressing the expresssion of specificity protein 1 in oral squamous cell carcinoma". International Journal of Molecular Medicine 32.4 (2013): 860-866.
Chicago
Jeon, Y., Ko, S. M., Cho, J. H., Chae, J., Shim, J."The HDAC inhibitor, panobinostat, induces apoptosis by suppressing the expresssion of specificity protein 1 in oral squamous cell carcinoma". International Journal of Molecular Medicine 32, no. 4 (2013): 860-866. https://doi.org/10.3892/ijmm.2013.1451
Copy and paste a formatted citation
x
Spandidos Publications style
Jeon Y, Ko SM, Cho JH, Chae J and Shim J: The HDAC inhibitor, panobinostat, induces apoptosis by suppressing the expresssion of specificity protein 1 in oral squamous cell carcinoma. Int J Mol Med 32: 860-866, 2013.
APA
Jeon, Y., Ko, S.M., Cho, J.H., Chae, J., & Shim, J. (2013). The HDAC inhibitor, panobinostat, induces apoptosis by suppressing the expresssion of specificity protein 1 in oral squamous cell carcinoma. International Journal of Molecular Medicine, 32, 860-866. https://doi.org/10.3892/ijmm.2013.1451
MLA
Jeon, Y., Ko, S. M., Cho, J. H., Chae, J., Shim, J."The HDAC inhibitor, panobinostat, induces apoptosis by suppressing the expresssion of specificity protein 1 in oral squamous cell carcinoma". International Journal of Molecular Medicine 32.4 (2013): 860-866.
Chicago
Jeon, Y., Ko, S. M., Cho, J. H., Chae, J., Shim, J."The HDAC inhibitor, panobinostat, induces apoptosis by suppressing the expresssion of specificity protein 1 in oral squamous cell carcinoma". International Journal of Molecular Medicine 32, no. 4 (2013): 860-866. https://doi.org/10.3892/ijmm.2013.1451
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