Induction of apoptosis by bleomycin in p53-null HL-60 leukemia cells
| Autor: | Emilie Landais, Hélène Bobichon, Françoise Liautaud-Roger, Delphine Gimonet, Paul Coninx |
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| Rok vydání: | 2004 |
| Předmět: |
Cancer Research
Antimetabolites Antineoplastic Time Factors Blotting Western Caspase 3 Apoptosis HL-60 Cells DNA Fragmentation Caspase 8 Amino Acid Chloromethyl Ketones Cell Line Bleomycin Bcl-2-associated X protein Proto-Oncogene Proteins Humans RNA Messenger Caspase bcl-2-Associated X Protein Leukemia biology Reverse Transcriptase Polymerase Chain Reaction Cytochrome c Intrinsic apoptosis Cytochromes c Genes p53 Molecular biology Mitochondria Enzyme Activation Microscopy Electron Phenotype Oncology Mitochondrial permeability transition pore Proto-Oncogene Proteins c-bcl-2 Caspases Cancer research biology.protein Cyclosporine RNA Tumor Suppressor Protein p53 Bongkrekic Acid |
| Zdroj: | International journal of oncology. 24(2) |
| ISSN: | 1019-6439 |
| Popis: | The role of p53 in apoptosis and the contrasting p53 status in tumors prompted us to investigate the bleomycin-induced apoptosis in p53-null human leukemia HL-60 cells (bleomycin at 160 microM for 7.5 h). Cells with apoptotic phenotype increased from 0.87% in controls to 9.40% in bleomycin-treated cells. Both the enzymes, caspase-3 and -8, were activated. Furthermore, the apoptotic phenotypes totally disappeared with zVAD-fmk, a caspase inhibitor. Besides, cytochrome c release from mitochondria happened simultaneously to apoptotic phenotypes, shrinkage of mitochondria but being independent of the mitochondrial permeability transition, since cyclosporine A and bongkrekic acid were inefficient on induced apoptosis. On the other hand, incubations with bleomycin (BLM) did not result in detectable changes in the expression of Bcl-2- and Bax-mRNA neither Bcl-2- or Bax-proteins. In conclusion, we suggest that BLM can produce apoptosis independently of p53 through three mechanisms: i) at the nuclear level by its endonuclease activities; ii) at the cell membrane, by activating caspases; and iii) at the mitochondria by releasing cytochrome c. These results indicate that BLM-induced apoptosis in HL-60 cells results from the activation of a mitochondria-dependent caspase cascade which includes also the activation of the initiator caspase-8. |
| Databáze: | OpenAIRE |
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