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


Cho, H; Koto, M; Riesterer, O; Molkentine, D P; Giri, U; Milas, L; Story, M D; Ha, C S; Raju, U (2009). Imexon augments sensitivity of human lymphoma cells to ionizing radiation: in vitro experimental study. Anticancer Research, 29(11):4409-4415.

Abstract

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.

Abstract

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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Radiation Oncology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2009
Deposited On:26 Jan 2010 10:52
Last Modified:05 Apr 2016 13:48
Publisher:International Institute of Anticancer Research
ISSN:0250-7005
Official URL:http://ar.iiarjournals.org/content/29/11/4409.abstract
PubMed ID:20032386

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