gms | German Medical Science

27th German Cancer Congress Berlin 2006

German Cancer Society (Frankfurt/M.)

22. - 26.03.2006, Berlin

Erucylphosphocholine and erucylphosphohomocholine increase sensitivity of human malignant glioma cell lines to the cytotoxic effects of ionizing radiation

Meeting Abstract

  • corresponding author presenting/speaker Amelie Rübel - Klinik für Radioonkologie, Tübingen, Deutschland
  • René Handrick - Klinik für Radioonkologie, Tübingen
  • Hansjörg Eibl - Max-Planck-institut für Biophysikalische Chemie, Göttingen
  • Wilfried Budach - Klinik für Radiookologie, Düsseldorf
  • Claus Belka - Klinik für Radioonkologie, Tübingen
  • Verena Jendrossek - Klinik für Radioonkologie, Tübingen

27. Deutscher Krebskongress. Berlin, 22.-26.03.2006. Düsseldorf, Köln: German Medical Science; 2006. DocPO452

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/dkk2006/06dkk562.shtml

Published: March 20, 2006

© 2006 Rübel et al.
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Outline

Text

Novel treatment concepts are badly needed to improve dismal prognosis of patients suffering from glioblastoma multiforme (GBM). We could recently demonstrate that Erucylphosphocholine (ErPC), the prototype of intravenously applicable antineoplastic alkylphosphocholines, potently induces apoptosis in highly resistant human astrocytoma/glioblastoma cell lines in vitro. Since ErPC is able to cross the blood brain barrier upon repeated intravenous injections in rats it constitutes a promising candidate for glioblastoma therapy. Aim of the present study was to analyze putative beneficial effects of ErPC and its clinically more advanced derivative erucylphosphohomocholine (ErPC3, ErufosineTM) on radiation-induced apoptosis and eradication of clonogenic tumor cells in human astrocytoma/ glioblastoma cell lines in vitro. Induction of apoptosis was evaluated in U87MG, A172 and T98G cells 24-72h after irradiation (2.5-10 Gy) with 6 MV photons from a linear accelerator and subsequent treatment with ErPC or ErPC3 (0-100µM). Cell death was quantified 24-72h after treatment by fluorescence microscopy using combined staining with Hoechst 33342 and propidium iodide. The biomathematical evaluation of putative additive or synergistic effects was performed by isobologram analysis. Eradication of clonogenic tumor cells was determined by standard colony formation assays. While all cell lines showed high intrinsic resistance against cytotoxic effects of ionizing radiation, treatment with ErPC and ErPC3 strongly increased sensitivity of the cells to radiation-induced cell death. T98G cells were most responsive to the combined treatment revealing highly synergistic effects while A172 showed mostly additive to synergistic effects and U87MG cells sub-additive, additive or synergistic effects, depending on the respective radiation-dose, drug-concentration and treatment time. Importantly, combined treatment increased radiation-induced eradication of clonogenic T98G cells as a clinically more relevant end point. Our observations make the combined treatment with ionizing radiation and ErPC or ErPC3 a promising approach for the treatment of patients suffering from malignant glioma. For a proof of concept, in vivo experiments in a xenograft model are under current investigation. Supported by the Deutsche Krebshilfe (10-1970 Be-III) and the fortune-program Universität Tübingen (126-0-0).