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

Michaelis, Martin, Suhan, Tatyana, Cinatl, Jaroslav, Driever, Pablo Hernáiz, Cinatl, Jindrich (2004) Valproic acid and interferon-alpha synergistically inhibit neuroblastoma cell growth in vitro and in vivo. International Journal of Oncology, 25 (6). pp. 1795-9. ISSN 1019-6439. (doi:10.3892/ijo.25.6.1795) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided)

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Official URL
http://dx.doi.org/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-alpha (IFN-alpha) in Be(2)-C neuroblastoma (NB) cells. Now, we studied the effects of VPA in combination with IFN-alpha on two other NB cell lines. UKF-NB-2 and UKF-NB-3 cell growth was synergistically inhibited by VPA and IFN-alpha. Cell cycle investigations revealed massive accumulation of cells in G0/G1-phase after a combined treatment with VPA and IFN-alpha. 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-alpha. Most strikingly, VPA plus IFN-alpha 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-alpha for NB patients.

Item Type: Article
DOI/Identification number: 10.3892/ijo.25.6.1795
Subjects: R Medicine > RM Therapeutics. Pharmacology
Divisions: Faculties > Sciences > School of Biosciences
Depositing User: Martin Michaelis
Date Deposited: 05 Jun 2013 20:24 UTC
Last Modified: 29 May 2019 10:15 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/34116 (The current URI for this page, for reference purposes)
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