Combination of fludarabine and imatinib induces apoptosis synergistically through loss of mitochondrial membrane potential and increases in caspase-3 enzyme activity in human K562 chronic myleloid leukemia cells

Cancer Invest. 2010 Jul;28(6):623-8. doi: 10.3109/07357901003631056.

Abstract

In this study, we aimed to show the synergistic apoptotic effects of imatinib/fludarabine combination in human K562 chronic myleloid leukemia (CML) cells. There was a significant increase in cytotoxicity of combination of imatinib and fludarabine as compared to any agent alone. On the other hand, combination of both agents induced apoptosis significantly as confirmed by increases in caspase-3 enzyme activity and decreases in mitochondrial membrane potential. As a summary, the results of this study strongly suggest that combination of imatinib and fludarabine induced cell death synergistically comparing to only imatinib or fludarabine in human K562 CML cells.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Apoptosis / drug effects*
  • Benzamides
  • Caspase 3 / metabolism*
  • Cell Death / drug effects
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Humans
  • Imatinib Mesylate
  • Inhibitory Concentration 50
  • K562 Cells
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology*
  • Membrane Potential, Mitochondrial / drug effects*
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Mitochondria / pathology
  • Piperazines / pharmacology
  • Pyrimidines / pharmacology
  • Vidarabine / analogs & derivatives
  • Vidarabine / pharmacology

Substances

  • Benzamides
  • Piperazines
  • Pyrimidines
  • Imatinib Mesylate
  • CASP3 protein, human
  • Caspase 3
  • Vidarabine
  • fludarabine