Apoptotic cytotoxic effects of a histone deacetylase inhibitor, FK228, on malignant lymphoid cells

Makoto Murata, Masayuki Towatari, Hiroshi Kosugi, Mitsune Tanimoto, Ryuzo Ueda, Hidehiko Saito, Tomoki Naoe

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41 Citations (Scopus)

Abstract

Histone deacetylases are promising targets for cancer treatment. Here we studied the in vitro effects of a potent histone deacetylase inhibitor, FK228 (formerly FR901228), on human leukemia/lymphoma cells and cell lines compared with normal hematopoietic cells. In a lymphoma cell line, Raji, a nanomolar concentration of FK228 induced G1 arrest and/or apoptotic cell death, depending on the concentration and exposure time. Growth of lymphoid cell lines including Raji (N=13) was inhibited by 50% (IC50) after 2-day treatment at concentrations of 0.83 to 1.87 ng/ml. Viability of clinical samples from patients with acute lymphoblastic leukemia was decreased by 50% at 0.78±0.46 ng/ml, whereas the IC50 values for normal mononuclear cells from peripheral blood and bone marrow were 2.3±0.96 and 7.8±1.0 ng/ml, respectively. The IC50 values for normal progenitor cells were 3.1, 4.4 and 7.8 ng/ml for BFU-E, CFU-GM and CFU-Mix, respectively. Expression levels of HDAC-1 and HDAC-3 proteins, which varied among cell lines, but were stable during the treatment with FK228, did not correlate with the sensitivity to FK288. This novel agent might be useful in the treatment of lymphoid malignancies, because the above concentrations are clinically achievable in vivo according to a recent clinical study.

Original languageEnglish
Pages (from-to)1154-1160
Number of pages7
JournalJapanese Journal of Cancer Research
Volume91
Issue number11
DOIs
Publication statusPublished - Jan 1 2000

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Keywords

  • Apoptosis
  • FK228
  • Histone deacetylase inhibitor
  • Leukemia
  • Lymphoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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