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Sodium valproate, a histone deacetylase inhibitor, decreases the secretion of soluble Fas by human osteosarcoma cells and increases their sensitivity to Fas-mediated cell death

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Abstract

Purpose

Effects of valproic acid (VPA), a histone deacetylase inhibitor, on the susceptibility to cell death induced by agonistic anti-Fas antibody were examined using four human osteosarcoma cell lines.

Method

Cell growth, secretion of soluble Fas, expression of cell-surface Fas, and sensitivity to Fas-mediated cell death were examined using cell proliferation assay, flow cytometry, enzyme-linked immunosorbent assay, and agonistic anti-Fas antibody, respectively.

Results

VPA suppressed the growth of all the four osteosarcoma cell lines and the secretion of soluble Fas from these cells. VPA showed no or slight suppressive effect on the expression of cell-surface Fas in the four osteosarcoma cell lines, but increased the sensitivity of three of four osteosarcoma cell lines to Fas-mediated cell death.

Conclusion

VPA enhances the susceptibility of human osteosarcoma cells to Fas-ligand-induced cell death by decreasing the secretion of soluble Fas and increasing the sensitivity to Fas-mediated cell death.

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Acknowledgments

This work was in part supported by a Grant-in-Aid for Young Scientists (B) (19791388) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, Grant-in-Aid for Researchers, Hyogo College of Medicine, a Hitec Research Center grant and Grant-in-Aid for Promotion of Technical Seeds in Advanced Medicine, Hyogo College of Medicine.

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Authors and Affiliations

  1. Department of Pathology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan

    Koji Yamanegi, Junko Yamane, Masaki Hata, Hideki Ohyama, Naoko Yamada, Nahoko Kato-Kogoe, Keiji Nakasho & Nobuyuki Terada

  2. Department of Orthopedic Surgery, Hyogo College of Medicine, Hyogo, Japan

    Hiroyuki Futani

  3. Laboratory of Host Defenses, Institute for Advanced Medical Sciences, Hyogo College of Medicine, Hyogo, Japan

    Haruki Okamura

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  1. Koji Yamanegi
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  2. Junko Yamane
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  3. Masaki Hata
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  4. Hideki Ohyama
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  9. Haruki Okamura
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  10. Nobuyuki Terada
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Correspondence to Koji Yamanegi.

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K. Yamanegi and J. Yamane are first authors who contributed equally to this work.

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Yamanegi, K., Yamane, J., Hata, M. et al. Sodium valproate, a histone deacetylase inhibitor, decreases the secretion of soluble Fas by human osteosarcoma cells and increases their sensitivity to Fas-mediated cell death. J Cancer Res Clin Oncol 135, 879–889 (2009). https://doi.org/10.1007/s00432-008-0522-z

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  • DOI: https://doi.org/10.1007/s00432-008-0522-z

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