The histone deacetylase inhibitor valproic acid alters growth properties of renal cell carcinoma in vitro and in vivo
- Histone deacetylase (HDAC) inhibitors represent a promising class of antineoplastic agents which affect tumour growth, differentiation and invasion. The effects of the HDAC inhibitor valproic acid (VPA) were tested in vitro and in vivo on pre-clinical renal cell carcinoma (RCC) models. Caki-1, KTC-26 or A498 cells were treated with various concentrations of VPA during in vitro cell proliferation 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays and to evaluate cell cycle manipulation. In vivo tumour growth was conducted in subcutaneous xenograft mouse models. The anti-tumoural potential of VPA combined with low-dosed interferon-α (IFN-α) was also investigated. VPA significantly and dose-dependently up-regulated histones H3 and H4 acetylation and caused growth arrest in RCC cells. VPA altered cell cycle regulating proteins, in particular CDK2, cyclin B, cyclin D3, p21 and Rb. In vivo, VPA significantly inhibited the growth of Caki-1 in subcutaneous xenografts, accompanied by a strong accumulation of p21 and bax in tissue specimens of VPA-treated animals. VPA–IFN-α combination markedly enhanced the effects of VPA monotherapy on RCC proliferation in vitro, but did not further enhance the anti-tumoural potential of VPA in vivo. VPA was found to have profound effects on RCC cell growth, lending support to the initiation of clinical testing of VPA for treating advanced RCC.
Author: | Jon JonesGND, Eva JüngelORCiDGND, Ausra Mickuckyte, Lukasz HudakGND, Steffen Alexander WedelGND, Dietger JonasGND, Roman A. BlahetaORCiD |
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URN: | urn:nbn:de:hebis:30:3-272767 |
DOI: | https://doi.org/10.1111/j.1582-4934.2008.00436.x |
ISSN: | 1582-4934 |
ISSN: | 1582-1838 |
Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/18657224 |
Parent Title (English): | Journal of cellular and molecular medicine |
Publisher: | Wiley-Blackwell |
Place of publication: | Hoboken, NJ |
Document Type: | Article |
Language: | English |
Date of Publication (online): | 2008/07/24 |
Date of first Publication: | 2008/07/24 |
Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Release Date: | 2013/02/08 |
Tag: | HDAC; proliferation; renal cell carcinoma; tumour growth; valproic acid |
Volume: | 13 |
Issue: | 8b |
Page Number: | 10 |
First Page: | 2376 |
Last Page: | 2385 |
Note: | © 2008 The Authors Journal compilation © 2009 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd. This is an Open Access article under the terms of the Creative Commons Attribution Non Commercial License http://creativecommons.org/licenses/by-nc/3.0/ which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
HeBIS-PPN: | 327689056 |
Institutes: | Medizin / Medizin |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Sammlungen: | Universitätspublikationen |
Licence (German): | Creative Commons - Namensnennung-Nicht kommerziell 3.0 |