Caspase independence of radio-induced cell death
| Autor: | Maria Castedo, D. Violot, Jean Bourhis, Yungan Tao, Guido Kroemer, Eric Deutsch, Ping Zhang, Didier Métivier |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Cancer Research
Programmed cell death Apoptosis Phosphatidylserines medicine.disease_cause Radiation Tolerance Amino Acid Chloromethyl Ketones chemistry.chemical_compound Multinucleate Genetics medicine Humans Radiosensitivity Clonogenic assay Molecular Biology Caspase biology Phosphatidylserine HCT116 Cells Caspase Inhibitors Enzyme Activation chemistry Gamma Rays Caspases Cancer research biology.protein Carcinogenesis |
| Zdroj: | Oncogene. 25:7758-7770 |
| ISSN: | 1476-5594 0950-9232 |
| DOI: | 10.1038/sj.onc.1209744 |
| Popis: | Colon carcinoma cells subjected to gamma-irradiation (4 Gy) manifest signs of apoptosis (caspase activation, chromatin condensation, phosphatidylserine (PS) exposure on the cell surface, sub-diploid DNA content), correlating with their radiosensitivity, which is increased in cells lacking the 14-3-3sigma protein as compared to wild-type controls. Inhibition of caspases by addition of Z-Val-Ala-DL-Asp (OMe)-fluoromethylketone, by stable transfection with the Baculovirus gene coding for p35, or by Bax knockout reduced all signs of apoptosis, yet failed to suppress radio-induced micro- and multinucleation. Moreover, pharmacological caspase inhibition, p35 expression or Bax knockout had no effect on the clonogenic survival that was reduced by gamma-irradiation and caspase inhibition failed to abolish the increased radiosensitivity of 14-3-3sigma-deficient cells. Micro- and multinucleation was detectable among non-apoptotic cells lacking PS exposure, as well as among cells undergoing apoptosis. Moreover, a fraction of micro- or multinucleated cells manifested caspase activation, and videomicroscopic analyses revealed that such cells could succumb to caspase-dependent apoptosis. Altogether, these results suggest that genomic instability induced by gamma-irradiation can trigger apoptosis, although apoptosis is dispensable for radio-induced clonogenic death. |
| Databáze: | OpenAIRE |
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