Control of Differentiation and Apoptosis of Human Myeloid Leukemia Cells by Cytokinins and Cytokinin Nucleosides, Plant Redifferentiation-Inducing Hormones

Cell Growth Differ. 2002 Jan;13(1):19-26.


We examined the effects of various adenine analogues on the growth and differentiation of human myeloid leukemia HL-60 cells. Some of these analogues inhibit growth and induce nitroblue tetrazolium reducing activity in HL-60 cells. Cytokinins such as kinetin, isopentenyladenine, and benzyladenine were very effective in inducing nitroblue tetrazolium reduction and morphological changes in the cells into mature granulocytes. On the other hand, cytokinin ribosides such as kinetin riboside, isopentenyladenosine, and benzylaminopurine riboside were the most potent for growth inhibition and apoptosis. Cytokinin ribosides greatly reduced the intracellular ATP content and disturbed the mitochondrial membrane potential and the accumulation of reactive oxygen species, whereas cytokinins did not. When the cells were incubated with cytokinin ribosides in the presence of O(2)(-) scavenger, antioxidant or caspase inhibitor, apoptosis was significantly reduced and differentiation was greatly enhanced. These results suggest that both cytokinins and cytokinin ribosides can induce granulocytic differentiation of HL-60 cells, but cytokinin ribosides also induce apoptosis prior to the differentiation process.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / analogs & derivatives
  • Adenosine / pharmacology*
  • Adenosine Triphosphate / analysis
  • Annexin A5 / metabolism
  • Antineoplastic Agents / pharmacology*
  • Antioxidants / metabolism
  • Apoptosis / drug effects*
  • Caspase 3
  • Caspases / analysis
  • Cell Differentiation / drug effects
  • Cell Division / drug effects
  • Cytokinins / pharmacology*
  • Granulocytes / pathology
  • HL-60 Cells
  • Humans
  • Leukemia, Myeloid / drug therapy*
  • Leukemia, Myeloid / metabolism
  • Leukemia, Myeloid / pathology
  • Macrophage-1 Antigen / metabolism
  • Muramidase / metabolism
  • Nitroblue Tetrazolium / metabolism
  • Reactive Oxygen Species / metabolism
  • Tumor Cells, Cultured


  • Annexin A5
  • Antineoplastic Agents
  • Antioxidants
  • Cytokinins
  • Macrophage-1 Antigen
  • Reactive Oxygen Species
  • Nitroblue Tetrazolium
  • Adenosine Triphosphate
  • Muramidase
  • CASP3 protein, human
  • Caspase 3
  • Caspases
  • Adenosine