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

Heunglae Cho, Masashi Koto, Oliver Riesterer, David P. Molkentine, Uma Giri, Luka Milas, Michael D. Story, Chul S. Ha, Uma Raju

Research output: Contribution to journalArticle

2 Citations (Scopus)

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 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.

Original languageEnglish (US)
Pages (from-to)4409-4415
Number of pages7
JournalAnticancer Research
Volume29
Issue number11
StatePublished - Nov 2009

Fingerprint

Ionizing Radiation
Lymphoma
Glutathione
Cell Cycle
Radiation Tolerance
Apoptosis
In Vitro Techniques
4-imino-1,3-diazabicyclo(3.1.0)hexan-2-one
Radiation
G2 Phase
Pancreatic Neoplasms
Caspase 3
Cell Division
Reactive Oxygen Species
Lung Neoplasms
Cell Survival
Western Blotting
Cell Proliferation
Clinical Trials
Cell Line

Keywords

  • Antiproliferative activity
  • Imexon antioxidant
  • Ionizing radiation
  • Lymphoma cells
  • Radiosensitization

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

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

Imexon augments sensitivity of human lymphoma cells to ionizing radiation : In vitro experimental study. / Cho, Heunglae; Koto, Masashi; Riesterer, Oliver; Molkentine, David P.; Giri, Uma; Milas, Luka; Story, Michael D.; Ha, Chul S.; Raju, Uma.

In: Anticancer Research, Vol. 29, No. 11, 11.2009, p. 4409-4415.

Research output: Contribution to journalArticle

Cho, H, Koto, M, Riesterer, O, Molkentine, DP, Giri, U, Milas, L, Story, MD, Ha, CS & Raju, U 2009, 'Imexon augments sensitivity of human lymphoma cells to ionizing radiation: In vitro experimental study', Anticancer Research, vol. 29, no. 11, pp. 4409-4415.
Cho H, Koto M, Riesterer O, Molkentine DP, Giri U, Milas L et al. Imexon augments sensitivity of human lymphoma cells to ionizing radiation: In vitro experimental study. Anticancer Research. 2009 Nov;29(11):4409-4415.
Cho, Heunglae ; Koto, Masashi ; Riesterer, Oliver ; Molkentine, David P. ; Giri, Uma ; Milas, Luka ; Story, Michael D. ; Ha, Chul S. ; Raju, Uma. / Imexon augments sensitivity of human lymphoma cells to ionizing radiation : In vitro experimental study. In: Anticancer Research. 2009 ; Vol. 29, No. 11. pp. 4409-4415.
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