Induction of apoptotic cell death by putrescine

Int J Biochem Cell Biol. 2006;38(4):621-8. doi: 10.1016/j.biocel.2005.10.020. Epub 2005 Dec 1.


The polyamines are essential for cellular growth and differentiation. Ornithine decarboxylase (ODC), which catalyses the first step in the biosynthesis of the polyamines, has a very fast turnover and is subject to a strong feedback control by the polyamines. In the present study, we show that overexpression of a metabolically stable ODC in CHO cells induced a massive cell death unless the cells were grown in the presence of the ODC inhibitor alpha-difluoromethylornithine (DFMO). Cells overexpressing wild-type (unstable) ODC, on the other hand, were not dependent on the presence of DFMO for their growth. The induction of cell death was correlated with a dramatic increase in cellular putrescine levels. Analysis using flow cytometry revealed perturbed cell cycle kinetics, with a large accumulation of cells with sub-G1 amounts of DNA, which is a typical sign of apoptosis. Another strong indication of apoptosis was the finding that one of the key enzymes in the apoptotic process, caspase-3, was induced when DFMO was omitted from the growth medium. Furthermore, inhibition of the caspase activity significantly reduced the recruitment of cells to the sub-G1 fraction. In conclusion, deregulation of polyamine homeostasis may negatively affect cell proliferation and eventually lead to cell death by apoptosis if putrescine levels become too high.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • CHO Cells
  • Caspase 3
  • Caspases / metabolism
  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects
  • Cricetinae
  • Cricetulus
  • Eflornithine / pharmacology
  • Enzyme Inhibitors
  • G1 Phase / drug effects
  • Ornithine Decarboxylase / metabolism
  • Ornithine Decarboxylase Inhibitors
  • Putrescine / biosynthesis
  • Putrescine / pharmacology*


  • Enzyme Inhibitors
  • Ornithine Decarboxylase Inhibitors
  • Caspase 3
  • Caspases
  • Ornithine Decarboxylase
  • Putrescine
  • Eflornithine