The mechanism of STI571 inducing apoptosis of K562 cells

Zhonghua Xue Ye Xue Za Zhi. 2002 Jun;23(6):289-92.

Abstract

Objective: To investigate the mechanism of STI571 inducing apoptosis of K562 cells which express P210(BCR/ABL).

Methods: Apoptosis was analyzed by Annexin-V/PI, DioC6 [3] staining, DCFH-DA staining, DNA-PI staining and DNA ladder. Western blot was used to analyse mitochondrial and cytosolic cyto C, Bcl-X(L), caspase-3, actin protein and the level of tyrosine phosphorylation.

Results: After exposure to STI571, K562 cells were induced to apoptosis. Tyrosine phosphorylation level of P210(BCR/ABL) and Bcl-X(L) was decreased. Caspase-3 was activated and there was an cytosolic accumulation of cyto C.

Conclusion: STI571 could rapidly decrease the tyrosine phosphorylation level of P210(BCR/ABL). The signal pathway mediated by the cytosolic translocation of mitochondrial cyto C was one of the mechanisms that STI571 inducing apoptosis. STI571 was an effective gene targeting therapeutic agent.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis*
  • Benzamides
  • Caspase 3
  • Caspases / metabolism
  • Cytochrome c Group / metabolism
  • Cytoplasm / metabolism
  • Enzyme Precursors / metabolism
  • Fusion Proteins, bcr-abl / metabolism
  • Humans
  • Imatinib Mesylate
  • K562 Cells
  • Membrane Potentials / drug effects
  • Mitochondria / drug effects
  • Piperazines / pharmacology*
  • Pyrimidines / pharmacology*
  • Reactive Oxygen Species / metabolism

Substances

  • Antineoplastic Agents
  • Benzamides
  • Cytochrome c Group
  • Enzyme Precursors
  • Piperazines
  • Pyrimidines
  • Reactive Oxygen Species
  • Imatinib Mesylate
  • Fusion Proteins, bcr-abl
  • CASP3 protein, human
  • Caspase 3
  • Caspases