Armeanu, S. and Pathil, A. and Venturelli, S. and Mascagni, P. and Weiss, Thomas S. and Goettlicher, M. and Gregor, M. and Lauer, U. M. and Bitzer, M. (2005) Apoptosis on hepatoma cells but not on primary hepatocytes by histone deacetylase inhibitors valproate and ITF2357. JOURNAL OF HEPATOLOGY, 42 (2). pp. 210-217. ISSN 0168-8278, 1600-0641
Full text not available from this repository. (Request a copy)Abstract
Background/Aims: Due to a particular resistance against conventional chemotherapeutics, palliative treatment of hepatocellular carcinomas (HCC) is highly ineffective. Recent demonstration of both proliferation-inhibition and apoptosis of hepatoma cells by a histone deacetylase inhibitor (HDAC-I) treatment opens up a promising new approach. However, little is known about tumor cell death mechanisms and HDAC-I influences on healthy hepatocytes. Methods: HDAC-I substances with favourable in vivo profiles, valproate (VPA) and ITF2357, were investigated on HCC cell lines and primary human hepatocytes (PHH). Histone acetylation and apoptosis-modulating proteins were investigated by western-blotting, proliferation by sulforhodamin B binding, toxicity by enzyme release, apoptosis by FACS analysis. Results: VPA and ITF2357 inhibited proliferation in HCC cell lines. Both substances induced considerable cellular damage in HCC-derived cells, but PHH tolerated these substances well. A downregulation of anti- and upregulation of proapoptotic factors was found. Moreover, Bcl-X-L transfection into HCC cells abrogated apoptosis induced by both substances, indicating that modulation of intracellular pro- and anti-apoptotic proteins is a key event in VPA or ITF2357 induced tumor-cell death. Conclusions: Preferential induction of cell death in HCC-derived cell lines, without toxicity in PHH, demonstrates the potential of VPA and ITF2357 to become promising new tools in the fight against HCC. (C) 2004 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HEPATOCELLULAR-CARCINOMA; TRANSFORMED-CELLS; HDAC INHIBITORS; ACID; DIFFERENTIATION; TRICHOSTATIN; ACTIVATION; EXPRESSION; INFECTION; CASPASE-8; hepatocellular carcinoma; histone code; cancer; programmed cell death; Bcl-2 proteins; hepatotoxicity |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Kinder- und Jugendmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 28 May 2021 12:01 |
| Last Modified: | 28 May 2021 12:01 |
| URI: | https://pred.uni-regensburg.de/id/eprint/36530 |
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