Mitochondria-independent morphological and biochemical apoptotic alterations promoted by the anti-tumor agent bleomycin in Saccharomyces cerevisiae.
Identifieur interne : 000155 ( France/Analysis ); précédent : 000154; suivant : 000156Mitochondria-independent morphological and biochemical apoptotic alterations promoted by the anti-tumor agent bleomycin in Saccharomyces cerevisiae.
Auteurs : Mustapha Aouida [France] ; Halima Mekid [France] ; Omrane Belhadj ; Lluis M. Mir [France] ; Omar Tounekti [France]Source :
- Biochemistry and Cell Biology [ 0829-8211 ] ; 2007-02.
Abstract
Bleomycin is a highly potent cytotoxic and genotoxic agent used in the chemotherapy of various types of tumors. It is a radiomimetic anticancer drug that produces single- and double-stranded DNA breaks in a catalytic way. Using Saccharomyces cerevisiae as a model system, we show that when a high amount of bleomycin molecules is internalized (100 micromol/L), morphological changes identical to those usually associated with apoptosis, i.e., a sub-G1 region peak, chromatin condensation, and very rapid DNA fragmentation into oligonucleosomal-sized fragments, are observed. The known bleomycin inhibitors cobalt and EDTA were able to prevent bleomycin nucleasic activity and thus apoptotic cell death. However, both oligomycin, a potent inhibitor of the mitochondrial F0F1-ATPase, and antimycin, a drug affecting mitochondria respiration, were unable to prevent the bleomycin-induced apoptotic-like cell death. These results suggest that high bleomycin concentrations induce an apoptosis-like mitochondria-independent cell death in yeast.
Url:
DOI: 10.1139/o06-147
Affiliations:
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Hal:hal-00158986Le document en format XML
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It is a radiomimetic anticancer drug that produces single- and double-stranded DNA breaks in a catalytic way. Using Saccharomyces cerevisiae as a model system, we show that when a high amount of bleomycin molecules is internalized (100 micromol/L), morphological changes identical to those usually associated with apoptosis, i.e., a sub-G1 region peak, chromatin condensation, and very rapid DNA fragmentation into oligonucleosomal-sized fragments, are observed. The known bleomycin inhibitors cobalt and EDTA were able to prevent bleomycin nucleasic activity and thus apoptotic cell death. However, both oligomycin, a potent inhibitor of the mitochondrial F0F1-ATPase, and antimycin, a drug affecting mitochondria respiration, were unable to prevent the bleomycin-induced apoptotic-like cell death. These results suggest that high bleomycin concentrations induce an apoptosis-like mitochondria-independent cell death in yeast.</div></front></TEI><affiliations><list><country><li>France</li></country></list><tree><noCountry><name sortKey="Belhadj, Omrane" sort="Belhadj, Omrane" uniqKey="Belhadj O" first="Omrane" last="Belhadj">Omrane Belhadj</name></noCountry><country name="France"><noRegion><name sortKey="Aouida, Mustapha" sort="Aouida, Mustapha" uniqKey="Aouida M" first="Mustapha" last="Aouida">Mustapha Aouida</name></noRegion><name sortKey="Mekid, Halima" sort="Mekid, Halima" uniqKey="Mekid H" first="Halima" last="Mekid">Halima Mekid</name><name sortKey="Mir, Lluis M" sort="Mir, Lluis M" uniqKey="Mir L" first="Lluis M" last="Mir">Lluis M. Mir</name><name sortKey="Tounekti, Omar" sort="Tounekti, Omar" uniqKey="Tounekti O" first="Omar" last="Tounekti">Omar Tounekti</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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