Document Detail


Imexon augments sensitivity of human lymphoma cells to ionizing radiation: in vitro experimental study.
MedLine Citation:
PMID:  20032386     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Imexon is an aziridine-containing small pro-oxidant molecule with promising antitumor activity in myeloma, lymphoma and lung and pancreatic cancer. Imexon is already in clinical trials in patients with advanced solid tumors. The present study examined the effects of imexon on H9 and Raji lymphoma cell lines in vitro when given in combination with ionizing radiation. MATERIALS AND METHODS: H9 and Raji lymphoma cells were grown in culture and exposed to imexon, radiation, or both. Cells were assessed for cell viability, glutathione content, induction of apoptosis, cell cycle distribution and also subject to Western blot analysis. RESULTS: Imexon inhibited cell proliferation in a dose-dependent manner. Imexon, given for 48 h prior to irradiation at a clinically achievable dose of 40 muM, potently enhanced the cell radiosensitivity. Imexon enhanced radiation-induced apoptosis and accumulated cells in G2/M phase of the cell cycle. Imexon induced caspase-3 activation and PARP cleavage. Alterations in glutathione levels were not observed at 40 microM of imexon. CONCLUSION: In conclusion, imexon efficiently augmented lymphoma cell radiosensitivity independently of glutathione and the underlying mechanisms include induction of apoptosis and cell cycle redistribution.
Authors:
Heunglae Cho; Masashi Koto; Oliver Riesterer; David P Molkentine; Uma Giri; Luka Milas; Michael D Story; Chul S Ha; Uma Raju
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Anticancer research     Volume:  29     ISSN:  1791-7530     ISO Abbreviation:  Anticancer Res.     Publication Date:  2009 Nov 
Date Detail:
Created Date:  2009-12-24     Completed Date:  2010-01-26     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8102988     Medline TA:  Anticancer Res     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  4409-15     Citation Subset:  IM    
Affiliation:
Department of Experimental Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / drug effects
Blotting, Western
Cell Cycle / drug effects
Cell Line, Tumor
Combined Modality Therapy
Hexanones / pharmacology*
Humans
Lymphoma, Non-Hodgkin / drug therapy*,  metabolism,  pathology,  radiotherapy*
Lymphoma, T-Cell / drug therapy*,  metabolism,  pathology,  radiotherapy*
Oxidation-Reduction
Radiation-Sensitizing Agents / pharmacology*
Chemical
Reg. No./Substance:
0/Hexanones; 0/Radiation-Sensitizing Agents; 59643-91-3/4-imino-1,3-diazabicyclo(3.1.0)hexan-2-one

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