Ajoene, an experimental anti-leukemic drug: mechanism of cell death
| Autor: | Angelika M. Vollmar, Dorothee Antlsperger, Verena M. Dirsch, Hannes Hentze |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Cancer Research
Apoptosis Amino Acid Chloromethyl Ketones Membrane Potentials Jurkat Cells chemistry.chemical_compound Disulfides Caspase Caspase 8 Enzyme Precursors Membrane Glycoproteins biology Caspase 3 Gene Expression Regulation Leukemic Cytochrome c NF-kappa B DNA Neoplasm Hematology Fas receptor Caspase 9 Mitochondria Neoplasm Proteins Cell biology Proto-Oncogene Proteins c-bcl-2 Oncology Biochemistry Caspases Sulfoxides Programmed cell death Fas Ligand Protein bcl-X Protein Cytochrome c Group HL-60 Cells DNA Fragmentation Cysteine Proteinase Inhibitors Permeability Humans Ajoene fas Receptor Plant Extracts Intracellular Membranes Antineoplastic Agents Phytogenic Enzyme Activation Oxidative Stress chemistry biology.protein Reactive Oxygen Species |
| Zdroj: | Leukemia. 16:74-83 |
| ISSN: | 1476-5551 0887-6924 |
| Popis: | The organosulfur compound ajoene, a constitutent of garlic, has been shown to induce apoptosis in a leukemic cell line as well as in blood cells of a leukemic patient. The mechanisms of action of ajoene, however, are unknown. The present study aims to characterize the molecular events leading to ajoene-triggered apoptosis. We show here that ajoene (20 microM) leads to a time-dependent activation of caspase-3-like activity as well as to the proteolytic processing of procaspase-3 and -8. Activation of caspases was necessary for ajoene-induced apoptosis since the broad-range caspase inhibitor zVAD-fmk completely abrogated ajoene-mediated DNA fragmentation. Although the initiator caspase-8 was activated, the CD95 death receptor was not involved in death signaling since the HL-60 clone used was shown to express a functionally inactive CD95 receptor. Furthermore, ajoene induced the release of cytochrome c, which was not inhibited by zVAD-fmk indicating that cytochrome c release precedes caspase activation. Ajoene also led to a dissipation of the mitochondrial transmembrane potential. Overexpression of Bcl-x(L) clearly diminished ajoene-induced caspase activation as well as apoptosis. These results indicate that apoptosis in leukemia cells triggered by ajoene is based on the activation of a mitochondria-dependent caspase cascade which includes also the activation of the initiator caspase-8. |
| Databáze: | OpenAIRE |
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