Nilotinib significantly induces apoptosis in imatinib-resistant K562 cells with wild-type BCR-ABL, as effectively as in parental sensitive counterparts

Hematology. 2010 Feb;15(1):33-8. doi: 10.1179/102453310X12583347009775.

Abstract

Chronic myeloid leukemia (CML) is a hematological malignancy characterized by high levels of immature white blood cells. CML is caused by the translocation between chromosomes 9 and 22 (which results in the formation of the Philadelphia chromosome) creating BCR-ABL fusion protein. Imatinib and nilotinib are chemotherapeutic drugs which specifically bind to the BCR-ABL and inhibit cancer cells. Nilotinib is more effective in this respect than imatinib. We have shown that nilotinib induces apoptosis in imatinib-resistant K562 CML cells which have the wild-type BCR-ABL fusion gene almost to the same extent as it does in the parental sensitive cells by the increase in caspase-3 enzyme activity and the decrease in mitochondrial membrane potential. This effect of nilotinib, even in low concentrations, may indicate the efficacy of the usage of nilotinib in imatinib-resistant CML with less risk of undesired cytotoxic effects in the remaining cells of the body.

Publication types

  • Comparative Study

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Base Sequence
  • Benzamides
  • Caspase 3 / metabolism
  • Cell Division / drug effects
  • Drug Resistance, Neoplasm
  • Drug Screening Assays, Antitumor
  • Fusion Proteins, bcr-abl / antagonists & inhibitors*
  • Fusion Proteins, bcr-abl / genetics
  • Humans
  • Imatinib Mesylate
  • Inhibitory Concentration 50
  • K562 Cells / cytology
  • K562 Cells / drug effects*
  • K562 Cells / enzymology
  • Membrane Potential, Mitochondrial / drug effects
  • Molecular Sequence Data
  • Neoplasm Proteins / antagonists & inhibitors*
  • Neoplasm Proteins / genetics
  • Piperazines / pharmacology*
  • Protein Kinase Inhibitors / pharmacology*
  • Pyrimidines / pharmacology*
  • Sequence Analysis, DNA

Substances

  • Antineoplastic Agents
  • Benzamides
  • Neoplasm Proteins
  • Piperazines
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Imatinib Mesylate
  • Fusion Proteins, bcr-abl
  • Caspase 3
  • nilotinib