p53-independent early and late apoptosis is mediated by ceramide after exposure of tumor cells to photon or carbon ion irradiation
| Autor: | Dominique Ardail, Priscillia Battiston-Montagne, Robert Rousson, Claudia Fournier, Claire Rodriguez-Lafrasse, Mira Maalouf, Gisela Taucher-Scholz, Gersende Alphonse, Michael Beuve |
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| Přispěvatelé: | Ciblage thérapeutique en Oncologie (EA3738), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Institut de Physique Nucléaire de Lyon (IPNL), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3), Groupe Hospitalier Est, Hospices Civils de Lyon (HCL), Biophysics Department [Darmstadt], Helmholtz Centre for Heavy Ion Research (GSI) |
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Ceramide
Pathology medicine.medical_specialty Cancer Research High- and low-LET-irradiation Apoptosis Ceramides Flow cytometry 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Radioresistance Cell Line Tumor Radiation Ionizing medicine Genetics Humans Radiosensitivity Mitotic catastrophe Caspase 030304 developmental biology 0303 health sciences Photons biology medicine.diagnostic_test Carbon ion irradiation p53-independent-apoptosis Dose-Response Relationship Radiation Carbon Mitochondria Kinetics chemistry Oncology Cell culture 030220 oncology & carcinogenesis Caspases biology.protein Cancer research Early and late apoptosis Tumor Suppressor Protein p53 Research Article |
| Zdroj: | BMC Cancer BMC Cancer, BioMed Central, 2013, 13, pp.151. ⟨10.1186/1471-2407-13-151⟩ |
| ISSN: | 1471-2407 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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