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

Eun Sun Choi, Gyoonhee Han, Song Kyu Park, Kiho Lee, Hyun Jung Kim, Sung Dae Cho, Hwan Mook Kim

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)195-200
Number of pages6
JournalMolecular Medicine Reports
Volume8
Issue number1
DOIs
Publication statusPublished - 2013 Jul 1

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Histone Deacetylase Inhibitors
Prostatic Neoplasms
Cells
Apoptosis
Proteins
Human Activities
Antineoplastic Agents
Cell Cycle
Down-Regulation
Western Blotting
Immunohistochemistry
Cell Line
Therapeutics
Growth

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Oncology
  • Cancer Research

Cite this

Choi, Eun Sun ; Han, Gyoonhee ; Park, Song Kyu ; Lee, Kiho ; Kim, Hyun Jung ; Cho, Sung Dae ; Kim, Hwan Mook. / A248, a novel synthetic HDAC inhibitor, induces apoptosis through the inhibition of specificity protein 1 and its downstream proteins in human prostate cancer cells. In: Molecular Medicine Reports. 2013 ; Vol. 8, No. 1. pp. 195-200.
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A248, a novel synthetic HDAC inhibitor, induces apoptosis through the inhibition of specificity protein 1 and its downstream proteins in human prostate cancer cells. / Choi, Eun Sun; Han, Gyoonhee; Park, Song Kyu; Lee, Kiho; Kim, Hyun Jung; Cho, Sung Dae; Kim, Hwan Mook.

In: Molecular Medicine Reports, Vol. 8, No. 1, 01.07.2013, p. 195-200.

Research output: Contribution to journalArticle

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