Original Articles Cellular and molecular portrait of eleven human glioblastoma cell lines under photon and carbon ion irradiation S. Ferrandon a , N. Magné a,b , P. Battiston-Montagne a , N.-H. Hau-Desbat a , O. Diaz a , M. Beuve c , J. Constanzo c , C. Chargari d , D. Poncet a,e , E. Chautard f , D. Ardail a,e , G. Alphonse a,e , C. Rodriguez-Lafrasse a,e, * a Laboratoire de Radiobiologie Cellulaire et Moléculaire, EMR3738, Faculté Médecine Lyon-Sud, Université de Lyon, Université Lyon1, 69921 Oullins, France b Départment de Radiothérapie, Institut de Cancérologie Lucien Neuwirth, 42271 St Priest-en-Jarez, France c IPNL-LIRIS-CNRS-IN2P3, 69622 Villeurbanne, France d Service de Radiothérapie, Hôpital du Val de Grâce, 75230 Paris, France e Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, 69495 Pierre-Bénite, France f Centre Jean Perrin, Laboratoire de Radio-Oncologie Expérimentale, Clermont Université, EA7283 CREaT, Université d’Auvergne, 63011 Clermont-Ferrand, France ARTICLE INFO Article history: Received 11 December 2014 Received in revised form 19 January 2015 Accepted 20 January 2015 Keywords: Glioblastoma Carbon beam Photon irradiation RBE Predictive marker A B ST R AC T This study aimed to examine the cellular and molecular long-term responses of glioblastomas to radiotherapy and hadrontherapy in order to better understand the biological effects of carbon beams in cancer treatment. Eleven human glioblastoma cell lines, displaying gradual radiosensitivity, were irradiated with photons or carbon ions. Independently of p53 or O 6 -methylguanine-DNA methyltransferase 1 status, all cell lines responded to irradiation by a G2/M phase arrest followed by the appearance of mitotic catastrophe, which was concluded by a ceramide-dependent-apoptotic cell death. Statistical analysis demonstrated that: (i) the SF2 2 and the D10 3 values for photon are correlated with that obtained in response to carbon ions; (ii) regardless of the p53, MGMT status, and radiosensitivity, the release of ceramide is associated with the induction of late apoptosis; and (iii) the appearance of polyploid cells after photon irradiation could predict the Relative Biological Efficiency 4 to carbon ions. This large collection of data should increase our knowledge in glioblastoma radiobiology in order to better understand, and to later individualize, appropriate radiotherapy treatment for patients who are good candidates. © 2015 Elsevier Ireland Ltd. All rights reserved. Introduction The glioblastoma multiform (GBM) is a heterogeneous and highly invasive entity, making it the most aggressive brain tumor. Even for selected patients receiving optimal surgery followed by temozolomide-based chemoradiotherapy according to the EORTC trial 26981/22981-NCIC, survival remains poor, with median sur- vival that does not exceed 15 months [1]. Over the past decade, a variety of different therapeutic strategies have been explored, however, a systemic targeted approach is partially limited by the heterogeneous biology of GBM and the low ability of most con- ventional cytotoxic drugs to cross the blood–brain barrier [2,3]. Due to a better dose localization in the tumor volume and a high relative biological effect (RBE) for cell killing, hadrontherapy with carbon ions seems to be particularly promising. Because very few hadrontherapy centers exist, the number of biological and clinical studies is limited. The results of a phase I/II clinical trial on pa- tients with GBM combining radiotherapy, chemotherapy, and carbon ion irradiation were promising in terms of progression-free and overall survival with relatively manageable toxicity [4]. Two other clinical trials are currently ongoing in order to better evaluate the efficiency of a carbon ion boost in GBM treatment [5,6]. Several in vitro studies have investigated the biological re- sponse of GBM cells to photon irradiation. Most of these studies focused on a limited aspect of the biological response and on only 2 or 3 cell lines [7,8]. These limitations are even more highlighted for hadrontherapy because of its novelty and the difficulty of access to platforms [9]. * Corresponding author. Tel.: +33(0)426235965; fax: +33(0)426235900. E-mail address: claire.rodriguez-lafrasse@univ-lyon1.fr (C. Rodriguez-Lafrasse). 1 MGMT: O 6 -methylguanine-DNA methyltransferase. 2 SF2: surviving fraction at 2Gy. 3 D10: dose for 10% survival. 4 RBE: Relative Biological Efficiency. http://dx.doi.org/10.1016/j.canlet.2015.01.025 0304-3835/© 2015 Elsevier Ireland Ltd. All rights reserved. Cancer Letters ■■ (2015) ■■–■■ ARTICLE IN PRESS Please cite this article in press as: S. Ferrandon, et al., Cellular and molecular portrait of eleven human glioblastoma cell lines under photon and carbon ion irradiation, Cancer Letters (2015), doi: 10.1016/j.canlet.2015.01.025 Contents lists available at ScienceDirect Cancer Letters journal homepage: www.elsevier.com/locate/canlet