A248, a novel synthetic HDAC inhibitor, induces apoptosis through the inhibition of specificity protein 1 and its downstream proteins in human prostate cancer cells

  • Authors:
    • Eun-Sun Choi
    • Gyoonhee Han
    • Song-Kyu Park
    • Kiho Lee
    • Hyun-Jung Kim
    • Sung-Dae Cho
    • Hwan Mook Kim
  • View Affiliations

  • Published online on: May 16, 2013     https://doi.org/10.3892/mmr.2013.1481
  • Pages: 195-200
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Abstract

Histone deacetylase (HDAC) inhibitors are emerging as potent anticancer agents due to their ability to induce apoptosis in various cancer cells, including prostate cancer cells. In the present study, we synthesized a novel HDAC inhibitor, A248, and investigated its apoptotic activity and molecular target in the DU145 and PC3 human prostate cancer cell lines. A248 inhibited the growth of DU145 and PC3 cells and induced apoptosis, as demonstrated by nuclear fragmentation and the accumulation of cells at subG1 phase of cell cycle. The treatment of DU145 and PC3 prostate cancer cells with A248 resulted in the downregulation of specificity protein 1 (Sp1) expression. Since the expression levels of survivin and Mcl-1 depend on Sp1, we also investigated the effects of A248 on survivin and Mcl-1 expression using western blot analysis and immunocytochemistry. The results showed that A248 markedly decreased the expression of survivin and Mcl-1. These data suggest that A248 has apoptotic activity in human prostate cancer cells and that Sp1 may be the molecular target of A248 treatment for inducing apoptosis in prostate cancer cells.
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July 2013
Volume 8 Issue 1

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Choi E, Han G, Park S, Lee K, Kim H, Cho S and Kim HM: A248, a novel synthetic HDAC inhibitor, induces apoptosis through the inhibition of specificity protein 1 and its downstream proteins in human prostate cancer cells. Mol Med Rep 8: 195-200, 2013
APA
Choi, E., Han, G., Park, S., Lee, K., Kim, H., Cho, S., & Kim, H.M. (2013). A248, a novel synthetic HDAC inhibitor, induces apoptosis through the inhibition of specificity protein 1 and its downstream proteins in human prostate cancer cells. Molecular Medicine Reports, 8, 195-200. https://doi.org/10.3892/mmr.2013.1481
MLA
Choi, E., Han, G., Park, S., Lee, K., Kim, H., Cho, S., Kim, H. M."A248, a novel synthetic HDAC inhibitor, induces apoptosis through the inhibition of specificity protein 1 and its downstream proteins in human prostate cancer cells". Molecular Medicine Reports 8.1 (2013): 195-200.
Chicago
Choi, E., Han, G., Park, S., Lee, K., Kim, H., Cho, S., Kim, H. M."A248, a novel synthetic HDAC inhibitor, induces apoptosis through the inhibition of specificity protein 1 and its downstream proteins in human prostate cancer cells". Molecular Medicine Reports 8, no. 1 (2013): 195-200. https://doi.org/10.3892/mmr.2013.1481