Imexon augments sensitivity of human lymphoma cells to ionizing radiation: in vitro experimental study.
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.


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.


CONCLUSIONS
In conclusion, imexon efficiently augmented lymphoma cell radiosensitivity independently of glutathione and the underlying mechanisms include induction of apoptosis and cell cycle redistribution.
Cho
Heunglae
H
Department of Experimental Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Koto
Masashi
M
Riesterer
Oliver
O
Molkentine
David P
DP
Giri
Uma
U
Milas
Luka
L
Story
Michael D
MD
Ha
Chul S
CS
Raju
Uma
U
D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D006588:Hexanones / Q000494:pharmacology*; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D016399:Lymphoma, T-Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D010084:Oxidation-Reduction; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*
D006588:Hexanones; D011838:Radiation-Sensitizing Agents; C014919:4-imino-1,3-diazabicyclo(3.1.0)hexan-2-one