Antitumor activity of the histone deacetylase inhibitor MS-275 in prostate cancer models

David Z. Qian, Yong Feng Wei, Xiaofei Wang, Yukihiko Kato, Linzhao Cheng, Roberto Pili

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

BACKGROUND. Histone deacetylase (HDAC) inhibitors represent a novel class of therapeutic agents with antitumor activity currently in clinical development. In this study, we tested the biological effects of the HDAC inhibitor MS-275 in various pre-clinical prostate cancer models both in vitro and in vivo. METHODS. In vitro cell proliferation XTT assay and protein expression analysis by Western blot were performed. In vivo tumor growth assessment in subcutaneous, orthotopic, and transgenic mouse models were conducted. RESULTS. MS-275 significantly upregulated histone H3 acetylation and p21 gene expression in human prostate cancer cell lines. MS-275 exerted growth arrest in PC-3 and LNCaP cells, and induced cell death in DU-145 cells. Prostate specific antigen protein levels were increased by MS-275 in LAPC4 cell line. In vivo, MS-275 inhibited the growth of DU-145, LNCaP, and PC-3 in subcutaneous xenografts. MS-275 had also a significant inhibition of PC-3 cells growth in a mouse intratibial model. Molecular analysis showed increased histone acetylation and p21 expression in tumor samples from MS-275-treated mice. In transgenic adenocarcinoma of mouse prostate (TRAMP) mice, long-term treatment of MS-275 slowed the progression of prostate carcinomas with significant reduction in cell proliferation. CONCLUSIONS. Taken together, these data support the clinical testing of MS-275 for the treatment of prostate cancer.

Original languageEnglish (US)
Pages (from-to)1182-1193
Number of pages12
JournalProstate
Volume67
Issue number11
DOIs
StatePublished - Aug 1 2007
Externally publishedYes

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Histone Deacetylase Inhibitors
Prostatic Neoplasms
Acetylation
Growth
Histones
Transgenic Mice
Prostate
Cell Proliferation
entinostat
Cell Line
Prostate-Specific Antigen
Heterografts
Antineoplastic Agents
Neoplasms
Proteins
Adenocarcinoma
Cell Death
Western Blotting
Carcinoma
Gene Expression

Keywords

  • Histone deacetylase inhibitor
  • Prostate cancer

ASJC Scopus subject areas

  • Urology

Cite this

Antitumor activity of the histone deacetylase inhibitor MS-275 in prostate cancer models. / Qian, David Z.; Wei, Yong Feng; Wang, Xiaofei; Kato, Yukihiko; Cheng, Linzhao; Pili, Roberto.

In: Prostate, Vol. 67, No. 11, 01.08.2007, p. 1182-1193.

Research output: Contribution to journalArticle

Qian, David Z. ; Wei, Yong Feng ; Wang, Xiaofei ; Kato, Yukihiko ; Cheng, Linzhao ; Pili, Roberto. / Antitumor activity of the histone deacetylase inhibitor MS-275 in prostate cancer models. In: Prostate. 2007 ; Vol. 67, No. 11. pp. 1182-1193.
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