YM-175 induces apoptosis of human native monocyte-lineage cells via inhibition of prenylation

Authors

  • Akiyoshi Miwa,

    1. Department of Hematology, National Center for Global Health and Medicine, Shinjyuku-ku, Tokyo 162-8655, Japan
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  • Naoki Takezako,

    Corresponding author
    1. Department of Biochemistry, Jichi Medical University, Shimotsuke-shi, Tochigi 329-0498, Japan
    2. Department of Hematology, National Hospital Organization Disaster Medical Center of Japan, Tachikawa-shi, Tokyo 190-0014, Japan
    3. Department of Medical Informatics, National Hospital Organization Disaster Medical Center of Japan, Tachikawa-shi, Tokyo 190-0014, Japan
    • Department of Medical Informatics, National Hospital Organization Disaster Medical Center of Japan, 3256 Midori-cho, Tachikawa City, Tokyo 190-0014, Japan
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  • Hiroko Hayakawa,

    1. Department of Biochemistry, Jichi Medical University, Shimotsuke-shi, Tochigi 329-0498, Japan
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  • Morisada Hayakawa,

    1. Department of Biochemistry, Jichi Medical University, Shimotsuke-shi, Tochigi 329-0498, Japan
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  • Shin-ichi Tominaga,

    1. Department of Biochemistry, Jichi Medical University, Shimotsuke-shi, Tochigi 329-0498, Japan
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  • Ken Yanagisawa

    1. Department of Biochemistry, Jichi Medical University, Shimotsuke-shi, Tochigi 329-0498, Japan
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Abstract

Nitrogen-containing bisphosphonates (NCBPs) have been widely used as standard supportive therapy to reduce skeletal-related events (SREs) in myeloma patients through suppression of osteoclast activity. In various prospective randomized trials that were performed following preliminary reports concerning efficacy, NCBPs have shown a significant beneficial effect on myeloma bone disease through both suppression of bone resorption and direct antimyeloma activity. Thus, NCBPs have an influence on many types of human cells. In this study, we examined the effect of an NCBP (YM-175) on an apoptosis of a monocytic cell line and of human native monocytes/macrophages and dendritic cells (DCs). We confirmed that monocytes, monocyte-derived macrophages, DCs, and a monoblastic cell line (THP-1) showed dose-dependent and time-dependent apoptosis related to the activation of caspases after exposure to YM-175 at concentrations below that at which the apoptosis of myeloma cell lines was induced. Such apoptosis of monocytic cells was suppressed by the addition of farnesol or geranylgeraniol. These findings suggest that the inhibition of monocyte-lineage cells or DCs by NCBPs might interfere with phagocytic activity or pathogen-presenting activity. Am. J. Hematol. 2012. © 2012 Wiley Periodicals, Inc.

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