Valproic acid cooperates with hydralazine to augment the susceptibility of human osteosarcoma cells to Fas- and NK cell-mediated cell death

  • Authors:
    • Koji Yamanegi
    • Junko Yamane
    • Kenta Kobayashi
    • Nahoko Kato-Kogoe
    • Hideki Ohyama
    • Keiji Nakasho
    • Naoko Yamada
    • Masaki Hata
    • Satoru Fukunaga
    • Hiroyuki Futani
    • Haruki Okamura
    • Nobuyuki Terada
  • View Affiliations

  • Published online on: April 19, 2012     https://doi.org/10.3892/ijo.2012.1438
  • Pages: 83-91
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

We investigated the effects of valproic acid (VPA), a histone deacetylase inhibitor, in combination with hydralazine, a DNA methylation inhibitor, on the expression of cell-surface Fas and MHC-class I-related chain molecules A and B (MICA and B), the ligands of NKG2D which is an activating receptor of NK cells, and on production of their soluble forms in HOS, U-2 OS and SaOS-2 human osteosarcoma cell lines. We also examined the susceptibility of these cells to Fas- and NK cell-mediated cell death. VPA did not increase the expression of Fas on the surface of osteosarcoma cells, while hydralazine did, and the combination of VPA with hydralazine increased the expression of cell-surface Fas. In contrast, the combination of VPA with hydralazine did not increase the production of soluble Fas by osteosarcoma cells. Both VPA and hydralazine increased the expression of cell-surface MICA and B in osteosarcoma cells, and their combination induced a greater increase in their expression. VPA inhibited the production of both soluble MICA and MICB by osteosarcoma cells while hydralazine produced no effect. Both VPA and hydralazine enhanced the susceptibility of osteosarcoma cells to Fas- and NK cell-mediated cell death and the combination of VPA with hydralazine further enhanced the effects. The present results suggest that combined administration of VPA and hydrazine is valuable for enhancing the therapeutic effects of immunotherapy for osteosarcomas.

Related Articles

Journal Cover

July 2012
Volume 41 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Yamanegi K, Yamane J, Kobayashi K, Kato-Kogoe N, Ohyama H, Nakasho K, Yamada N, Hata M, Fukunaga S, Futani H, Futani H, et al: Valproic acid cooperates with hydralazine to augment the susceptibility of human osteosarcoma cells to Fas- and NK cell-mediated cell death. Int J Oncol 41: 83-91, 2012.
APA
Yamanegi, K., Yamane, J., Kobayashi, K., Kato-Kogoe, N., Ohyama, H., Nakasho, K. ... Terada, N. (2012). Valproic acid cooperates with hydralazine to augment the susceptibility of human osteosarcoma cells to Fas- and NK cell-mediated cell death. International Journal of Oncology, 41, 83-91. https://doi.org/10.3892/ijo.2012.1438
MLA
Yamanegi, K., Yamane, J., Kobayashi, K., Kato-Kogoe, N., Ohyama, H., Nakasho, K., Yamada, N., Hata, M., Fukunaga, S., Futani, H., Okamura, H., Terada, N."Valproic acid cooperates with hydralazine to augment the susceptibility of human osteosarcoma cells to Fas- and NK cell-mediated cell death". International Journal of Oncology 41.1 (2012): 83-91.
Chicago
Yamanegi, K., Yamane, J., Kobayashi, K., Kato-Kogoe, N., Ohyama, H., Nakasho, K., Yamada, N., Hata, M., Fukunaga, S., Futani, H., Okamura, H., Terada, N."Valproic acid cooperates with hydralazine to augment the susceptibility of human osteosarcoma cells to Fas- and NK cell-mediated cell death". International Journal of Oncology 41, no. 1 (2012): 83-91. https://doi.org/10.3892/ijo.2012.1438