Comparison of burst of reactive oxygen species and activation of caspase-3 in apoptosis of K562 and HL-60 cells induced by docetaxel

Cancer Lett. 2004 Oct 8;214(1):103-13. doi: 10.1016/j.canlet.2004.03.047.

Abstract

Apoptosis-resistant K562 cells and apoptosis-proficient HL-60 acute myelomonocytic leukemia cells were selected to study the cell-type-specific characteristics of docetaxel. The kinetics of cytotoxicity of docetaxel showed a delayed response of K562 cells compared to HL-60 cells. After treatment with 10(-8)M docetaxel, DNA fragmentation and sub-G0/G1 cells were evident in HL-60 cells in less than 6 h, while K562 cells gradually arrested in G2/M phase of the cell cycle and appeared normal for 24 h before developing similar apoptotic changes. The delayed apoptotic changes in K562 cells were accompanied by delayed activation of caspase-3. Additionally, NADPH oxidase inhibition with diphenylene iodonium showed that reactive oxygen species (ROS) burst mediated critically in the caspase-3 activation and apoptosis in HL-60 cells but was only partially involved in those events of K562 cells. These results suggested that docetaxel exposure triggered the delayed apoptosis in K562 cells and the different ROS-dependent or independent signal pathways might account for this phenomenon. Docetaxel elicited ROS production from NADPH oxidase, which in turn triggered activation of caspase-3, leading to apoptosis in HL-60 cells. While in K562 cells, docetaxel induced apoptosis after G2/M accumulation through ROS-independent or partially dependent pathways.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects*
  • Caspase 3
  • Caspases / biosynthesis*
  • Docetaxel
  • Enzyme Induction
  • HL-60 Cells
  • Humans
  • K562 Cells
  • Kinetics
  • Reactive Oxygen Species*
  • Taxoids / pharmacology*

Substances

  • Antineoplastic Agents, Phytogenic
  • Reactive Oxygen Species
  • Taxoids
  • Docetaxel
  • CASP3 protein, human
  • Caspase 3
  • Caspases