L'apoptose induite par les medicaments antileucemiques: Le parcours d'obstacles

Éric Solary, Ali Bettaieb, Carmen Garrido

Résultats de recherche: Contribution à un journalArticle 'review'Revue par des pairs

1 Citation (Scopus)

Résumé

Apoptosis is the principal mode of cell death triggered by cytotoxic drugs. At the molecular level, drug-induced apoptosis involves the mitochondrial release of cytochrome c that combines in the cytosol with APAF- 1 in the presence of ATP to activate procaspase-9. In turn, caspase 9 activates effector caspases such as procaspase-3. Activation of this apoptotic machinery can be delayed or inhibited by oncogenic proteins such as Bcl-2 and Bcr-abl, cell cycle regulatory proteins such as p27(Kip1) and protein kinases such as protein kinase C and phosphatidyli-nositol-3-klnase. Antisense oligonucleotides and chemical inhibitors targeting these molecules could be used to increase drug-induced cell death. Cytotoxic agents modulate also death, pathways involving the so-called 'death receptors' at the plasma membrane level. At low doses, they sensitize tumor cells to CD95-mediated apoptosis by upregulating the expression of CD95 (Fas/Apo-1) receptor, the adaptator molecule FADD and several downstream procaspases. This observation provides a rational for the sequential use of cytotoxic agents and immunotherapy. Lastly, chemotherapeutic drugs upregulate CD95-ligand expression in leukemic cells. Interaction of CD95-ligand with its receptor at the surface of tumor cells has been proposed to contribute to drug-induced cell death. This review summarizes the substantial progresses in cell death mechanism understanding and suggests strategies for a more efficient and less toxic use of antileukemic agents.

Titre traduit de la contributionApoptosis induced by antileukemic agents
langue originaleFrançais
Pages (de - à)43-52
Nombre de pages10
journalHematologie
Volume5
Numéro de publication1
étatPublié - 1 janv. 1999
Modification externeOui

mots-clés

  • Apoptosis
  • Caspases
  • Cell cycle
  • Cytotoxic drugs
  • Death receptors
  • Leukemia
  • Signal transduction

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