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Title: Enhancement of Radiation Response in Osteosarcoma and Rhabomyosarcoma Cell Lines by Histone Deacetylase Inhibition

Abstract

Purpose: Histone deacetylase inhibitors (HDACIs) can enhance the sensitivity of cells to photon radiation treatment (XRT) by altering numerous molecular pathways. We investigated the effect of pan-HDACIs such as suberoylanilide hydroxamic acid (SAHA) on radiation response in two osteosarcoma (OS) and two rhabdomyosarcoma (RMS) cell lines. Methods and Materials: Clonogenic survival, cell cycle analysis, and apoptosis were examined in OS (KHOS-24OS, SAOS2) and RMS (A-204, RD) cell lines treated with HDACI and HDACI plus XRT, respectively. Protein expression was investigated via immunoblot analysis, and cell cycle analysis and measurement of apoptosis were performed using flow cytometry. Results: SAHA induced an inhibition of cell proliferation and clonogenic survival in OS and RMS cell lines and led to a significant radiosensitization of all tumor cell lines. Other HDACI such as M344 and valproate showed similar effects as investigated in one OS cell line. Furthermore, SAHA significantly increased radiation-induced apoptosis in the OS cell lines, whereas in the RMS cell lines radiation-induced apoptosis was insignificant with and without SAHA. In all investigated sarcoma cell lines, SAHA attenuated radiation-induced DNA repair protein expression (Rad51, Ku80). Conclusion: Our results show that HDACIs enhance radiation action in OS and RMS cell lines. Inhibition of DNA repair,more » as well as increased apoptosis induction after exposure to HDACIs, can be mechanisms of radiosensitization by HDACIs.« less

Authors:
 [1];  [2];  [3]
  1. Department of Pediatric Oncology, Hematology, Immunology and Pulmology, University of Heidelberg (Germany)
  2. Department of Radiation Oncology, University of Heidelberg (Germany)
  3. Institute of Pathology, University of Heidelberg (Germany)
Publication Date:
OSTI Identifier:
21451152
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 78; Journal Issue: 1; Other Information: DOI: 10.1016/j.ijrobp.2010.03.010; PII: S0360-3016(10)00414-1; Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; APOPTOSIS; CELL CYCLE; CELL PROLIFERATION; CONNECTIVE TISSUE CELLS; HYDROXAMIC ACIDS; INHIBITION; OSTEOSARCOMAS; RADIOSENSITIVITY EFFECTS; RADIOTHERAPY; TUMOR CELLS; AMINES; ANIMAL CELLS; DISEASES; HYDROXY COMPOUNDS; MEDICINE; NEOPLASMS; NUCLEAR MEDICINE; ORGANIC COMPOUNDS; RADIOLOGY; SARCOMAS; SKELETAL DISEASES; SOMATIC CELLS; THERAPY

Citation Formats

Blattmann, Claudia, E-mail: claudia.blattmann@med.uni-heidelberg.d, Oertel, Susanne, and Ehemann, Volker. Enhancement of Radiation Response in Osteosarcoma and Rhabomyosarcoma Cell Lines by Histone Deacetylase Inhibition. United States: N. p., 2010. Web. doi:10.1016/j.ijrobp.2010.03.010.
Blattmann, Claudia, E-mail: claudia.blattmann@med.uni-heidelberg.d, Oertel, Susanne, & Ehemann, Volker. Enhancement of Radiation Response in Osteosarcoma and Rhabomyosarcoma Cell Lines by Histone Deacetylase Inhibition. United States. doi:10.1016/j.ijrobp.2010.03.010.
Blattmann, Claudia, E-mail: claudia.blattmann@med.uni-heidelberg.d, Oertel, Susanne, and Ehemann, Volker. Wed . "Enhancement of Radiation Response in Osteosarcoma and Rhabomyosarcoma Cell Lines by Histone Deacetylase Inhibition". United States. doi:10.1016/j.ijrobp.2010.03.010.
@article{osti_21451152,
title = {Enhancement of Radiation Response in Osteosarcoma and Rhabomyosarcoma Cell Lines by Histone Deacetylase Inhibition},
author = {Blattmann, Claudia, E-mail: claudia.blattmann@med.uni-heidelberg.d and Oertel, Susanne and Ehemann, Volker},
abstractNote = {Purpose: Histone deacetylase inhibitors (HDACIs) can enhance the sensitivity of cells to photon radiation treatment (XRT) by altering numerous molecular pathways. We investigated the effect of pan-HDACIs such as suberoylanilide hydroxamic acid (SAHA) on radiation response in two osteosarcoma (OS) and two rhabdomyosarcoma (RMS) cell lines. Methods and Materials: Clonogenic survival, cell cycle analysis, and apoptosis were examined in OS (KHOS-24OS, SAOS2) and RMS (A-204, RD) cell lines treated with HDACI and HDACI plus XRT, respectively. Protein expression was investigated via immunoblot analysis, and cell cycle analysis and measurement of apoptosis were performed using flow cytometry. Results: SAHA induced an inhibition of cell proliferation and clonogenic survival in OS and RMS cell lines and led to a significant radiosensitization of all tumor cell lines. Other HDACI such as M344 and valproate showed similar effects as investigated in one OS cell line. Furthermore, SAHA significantly increased radiation-induced apoptosis in the OS cell lines, whereas in the RMS cell lines radiation-induced apoptosis was insignificant with and without SAHA. In all investigated sarcoma cell lines, SAHA attenuated radiation-induced DNA repair protein expression (Rad51, Ku80). Conclusion: Our results show that HDACIs enhance radiation action in OS and RMS cell lines. Inhibition of DNA repair, as well as increased apoptosis induction after exposure to HDACIs, can be mechanisms of radiosensitization by HDACIs.},
doi = {10.1016/j.ijrobp.2010.03.010},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 1,
volume = 78,
place = {United States},
year = {Wed Sep 01 00:00:00 EDT 2010},
month = {Wed Sep 01 00:00:00 EDT 2010}
}