A novel time resolved fluorometric assay of anoikis using Europium-labelled Annexin V in cultured adherent cells

Apoptosis. 2005 Mar;10(2):429-37. doi: 10.1007/s10495-005-0816-4.

Abstract

Background: Adherent cells undergo apoptosis when detached from their home ground, a process called anoikis (homelessness).

Methods: We developed a new and sensitive method to analyse apoptosis and anoikis of adherent cell types using a time resolved fluorometric assay with Europium-labelled Annexin V. Anoikis was induced with tumor necrosis factor-alpha/cycloheximide and three cell fractions of the cell cultures were prepared and analysed. Fraction 1 consisted of adherent cells, analysed while growing on their support (without detachment by trypsinisation). Fraction 2 contained detached cells due to anoikis (floating cells) and fraction 3 contained apoptotic bodies. Both fractions 2 and 3 were present in the culture medium and were isolated by differential centrifugation.

Results: TNF-alpha treatment of three different types of adherent cell cultures induced a significant increase of the amount of floating cells (anoikis) and apoptotic bodies compared to control cell cultures. Also in the adherent cell fractions a small amount of apoptosis was observed.

Conclusions: The novel time resolved assay provides the ability to analyse the cell death cascade in adherent cell cultures of the same sample at the same time in a sensitive and reproducible way.

MeSH terms

  • Annexin A5 / pharmacology*
  • Anoikis*
  • Apoptosis
  • Cell Adhesion
  • Cell Culture Techniques / methods
  • Cells, Cultured
  • Coloring Agents / pharmacology*
  • Culture Media / pharmacology
  • DNA Fragmentation
  • Endothelium, Vascular / cytology
  • Enzyme Inhibitors / pharmacology
  • Europium / pharmacology*
  • Flow Cytometry
  • Humans
  • Microcirculation
  • Myocytes, Smooth Muscle / cytology
  • Sensitivity and Specificity
  • Spectrometry, Fluorescence / methods*
  • Time Factors
  • Trypsin / pharmacology
  • Tumor Necrosis Factor-alpha / metabolism
  • Umbilical Veins / cytology

Substances

  • Annexin A5
  • Coloring Agents
  • Culture Media
  • Enzyme Inhibitors
  • Tumor Necrosis Factor-alpha
  • Europium
  • Trypsin