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BMC Cancer
Published in: BMC Cancer 1/2013

Open Access 01-12-2013 | Research article

p53-independent early and late apoptosis is mediated by ceramide after exposure of tumor cells to photon or carbon ion irradiation

Authors: Gersende Alphonse, Mira Maalouf, Priscillia Battiston-Montagne, Dominique Ardail, Michaël Beuve, Robert Rousson, Gisela Taucher-Scholz, Claudia Fournier, Claire Rodriguez-Lafrasse

Published in: BMC Cancer | Issue 1/2013

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Abstract

Background

To determine whether ceramide is responsible for the induction of p53-independent early or late apoptosis in response to high- and low-Linear-Energy-Transfer (LET) irradiation.

Methods

Four cell lines displaying different radiosensitivities and p53-protein status were irradiated with photons or 33.4 or 184 keV/μm carbon ions. The kinetics of ceramide production was quantified by fluorescent microscopy or High-Performance-Liquid-Chromatogaphy and the sequence of events leading to apoptosis by flow cytometry.

Results

Regardless of the p53-status, both low and high-LET irradiation induced an early ceramide production in radiosensitive cells and late in the radioresistant. This production strongly correlated with the level of early apoptosis in radiosensitive cells and delayed apoptosis in the radioresistant ones, regardless of radiation quality, tumor type, radiosensitivity, or p53-status. Inhibition of caspase activity or ceramide production showed that, for both types of radiation, ceramide is essential for the initiation of early apoptosis in radiosensitive cells and late apoptosis following mitotic catastrophe in radioresistant cells.

Conclusions

Ceramide is a determining factor in the onset of early and late apoptosis after low and high-LET irradiation and is the mediator of the p53-independent-apoptotic pathway. We propose that ceramide is the molecular bridge between mitotic catastrophe and the commitment phase of delayed apoptosis in response to irradiation.
Appendix
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Metadata
Title
p53-independent early and late apoptosis is mediated by ceramide after exposure of tumor cells to photon or carbon ion irradiation
Authors
Gersende Alphonse
Mira Maalouf
Priscillia Battiston-Montagne
Dominique Ardail
Michaël Beuve
Robert Rousson
Gisela Taucher-Scholz
Claudia Fournier
Claire Rodriguez-Lafrasse
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2013
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-13-151

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