RT Journal Article SR Electronic T1 Imexon Augments Sensitivity of Human Lymphoma Cells to Ionizing Radiation: In Vitro Experimental Study JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 4409 OP 4415 VO 29 IS 11 A1 HEUNGLAE CHO A1 MASASHI KOTO A1 OLIVER RIESTERER A1 DAVID P. MOLKENTINE A1 UMA GIRI A1 LUKA MILAS A1 MICHAEL D. STORY A1 CHUL S. HA A1 UMA RAJU YR 2009 UL http://ar.iiarjournals.org/content/29/11/4409.abstract AB 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 μM, 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 μM 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.