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

    51 Scopus citations

    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

    Keywords

    • Histone deacetylase inhibitor
    • Prostate cancer

    ASJC Scopus subject areas

    • Oncology
    • Urology

    Fingerprint Dive into the research topics of 'Antitumor activity of the histone deacetylase inhibitor MS-275 in prostate cancer models'. Together they form a unique fingerprint.

  • Cite this