Valproic acid and interferon-α synergistically inhibit neuroblastoma cell growth in vitro and in vivo

  • Authors: Martin Michaelis, Tatyana Suhan, Jaroslav Cinatl, Pablo Hernáiz Driever, Jindrich Cinatl
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  • Published online on: Wednesday, December 1, 2004
  • Pages: 1795-1799
  • DOI: 10.3892/ijo.25.6.1795

Abstract

Valproic acid (VPA) as a differentiation inducing anti-neoplastic substance is currently tested in solid tumour and leukaemia patients. Previously, we were able to show that the anti-cancer activity of VPA was synergistically increased by interferon-α (IFN-α) in Be(2)-C neuroblastoma (NB) cells. Now, we studied the effects of VPA in combination with IFN-α on two other NB cell lines. UKF-NB-2 and UKF-NB-3 cell growth was synergistically inhibited by VPA and IFN-α. Cell cycle investigations revealed massive accumulation of cells in G0/G1-phase after a combined treatment with VPA and IFN-α. The VPA-induced accumulation of acetylated histones in NB cell nuclei that indicates inhibition of histone deacetylases was not further enhanced by the combination treatment with IFN-α. Most strikingly, VPA plus IFN-α synergistically inhibited growth of UKF-NB-3 xenograft tumours in nude mice and induced complete cures in two out of six animals, while single treatment merely inhibited tumour growth. The results of this study together with our previous report strongly encourage the clinical evaluation of VPA and IFN-α for NB patients.
Journal Cover

December 2004
Volume 25 Issue 6

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

2012 Impact Factor: 2.773
Ranked #30/202 Oncology
(total number of cites)

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APA
Michaelis, M., Suhan, T., Cinatl, J., Driever, P., & Cinatl, J. (2004). Valproic acid and interferon-α synergistically inhibit neuroblastoma cell growth in vitro and in vivo. International Journal of Oncology, 25(6), 1795-1799.
MLA
Michaelis, Suhan, Cinatl, Driever, and Jindrich Cinatl. "Valproic acid and interferon-α synergistically inhibit neuroblastoma cell growth in vitro and in vivo." International Journal of Oncology International Journal of Oncology 25.6 (2004): 1795-1799.
Chicago
Michaelis, Suhan, Cinatl, Driever, and Jindrich Cinatl. "Valproic acid and interferon-α synergistically inhibit neuroblastoma cell growth in vitro and in vivo." International Journal of Oncology International Journal of Oncology 25 no. 6 (2004): 1795-1799.