TY  - JOUR
A1  - Jones, Jon
A1  - Jüngel, Eva
A1  - Mickuckyte, Ausra
A1  - Hudak, Lukasz
A1  - Wedel, Steffen Alexander
A1  - Jonas, Dietger
A1  - Blaheta, Roman A.
T1  - The histone deacetylase inhibitor valproic acid alters growth properties of renal cell carcinoma in vitro and in vivo
T2  - Journal of cellular and molecular medicine
N2  - 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.
KW  - HDAC
KW  - valproic acid
KW  - renal cell carcinoma
KW  - proliferation
KW  - tumour growth
Y1  - 2008
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/27276
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-272767
SN  - 1582-4934
SN  - 1582-1838
N1  - © 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.
VL  - 13
IS  - 8b
SP  - 2376
EP  - 2385
PB  - Wiley-Blackwell
CY  - Hoboken, NJ
ER  -