Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/38792
Type: Journal article
Title: Histone deacetylase inhibitors induce growth suppression and cell death in human rhabdomyosarcoma in vitro
Author: Kutko, M.
Glick, R.
Butler, L.
Coffey, D.
Rifkind, R.
Marks, P.
Richon, V.
LaQuaglia, M.
Citation: Clinical Cancer Research, 2003; 9(15):5749-5755
Publisher: Amer Assoc Cancer Research
Issue Date: 2003
ISSN: 1078-0432
Statement of
Responsibility: 
Martha C. Kutko, Richard D. Glick, Lisa M. Butler, Dennis C. Coffey, Richard A. Rifkind, Paul A. Marks, Victoria M. Richon, and Michael P. LaQuaglia
Abstract: Purpose: A group of histone deacetylase inhibitors has been shown to be effective in suppressing the growth of a variety of transformed cell lines in vitro and in vivo. The effects of two of these agents, suberoylanilide hydroxamic acid (SAHA) and suberoyl-3-aminopyridineamide hydroxamic acid (pyroxamide), were investigated for their growth-suppressive effects on rhabdomyosarcoma (RMS) cells. Experimental Design and Results: Dose-response experiments of two RMS cell lines, RD (embryonal) and RH30B (alveolar), were performed with SAHA (0.25–3.0 μm) and pyroxamide (1.25–20.0 μm). Both agents caused a dose-dependent decrease in viable cell number and an increase in percentage of dead cells over time. Exposure of the RMS cells to SAHA and pyroxamide resulted in an accumulation of acetylated histones with increasing doses by Western blot analysis. Additionally, there was an induction of p21/WAF1 at 15 and 24 h when the cells were cultured with SAHA (2.0 μm) or pyroxamide (20.0 μm), concentrations that were tested because they successfully induced inhibition of cell growth and initiated cell death in both RMS cell lines. An increase in nuclei with hypodiploid or sub-G1 fraction was found by flow cytometry with increasing doses of both SAHA (0.25–3.0 μm) and pyroxamide (1.25–20.0 μm) over time. This finding is consistent with DNA fragmentation and cell death by apoptosis. Conclusions: SAHA and pyroxamide induce growth suppression and cell death in human RMS in vitro. Accumulation of acetylated histones and induction of p21/WAF1 expression are observed in cells exposed to either agent.
Keywords: Cell Line, Tumor; Humans; Rhabdomyosarcoma; Histones; Enzyme Inhibitors; Flow Cytometry; Cell Division; Cell Death; Acetylation; Kinetics; Histone Deacetylase Inhibitors
Description: © 2003 American Association for Cancer Research
RMID: 0020071650
Published version: http://clincancerres.aacrjournals.org/content/9/15/5749.full
Appears in Collections:Medicine publications

Files in This Item:
There are no files associated with this item.


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.