Cellular and molecular portrait of eleven human glioblastoma cell lines under photon and carbon ion irradiation

Cancer Lett. 2015 Apr 28;360(1):10-6. doi: 10.1016/j.canlet.2015.01.025. Epub 2015 Feb 2.

Abstract

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.

Keywords: Carbon beam; Glioblastoma; Photon irradiation; Predictive marker; RBE.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / radiation effects
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology
  • Brain Neoplasms / radiotherapy*
  • Ceramides / metabolism
  • DNA Modification Methylases / genetics
  • DNA Modification Methylases / metabolism
  • DNA Repair Enzymes / genetics
  • DNA Repair Enzymes / metabolism
  • G2 Phase Cell Cycle Checkpoints / radiation effects
  • Glioblastoma / genetics
  • Glioblastoma / metabolism
  • Glioblastoma / pathology
  • Glioblastoma / radiotherapy*
  • Heavy Ion Radiotherapy*
  • Humans
  • Kinetics
  • Mitosis / radiation effects
  • Photons*
  • Radiation Tolerance
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism

Substances

  • Ceramides
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins
  • DNA Modification Methylases
  • MGMT protein, human
  • DNA Repair Enzymes