Metaphase arrest and cell death induced by etoposide on HeLa cells

Int J Biochem Cell Biol. 2006;38(12):2183-95. doi: 10.1016/j.biocel.2006.06.013. Epub 2006 Jul 18.


DNA damage, cell cycle and apoptosis form a network with important implications for cancer chemotherapy. Dysfunctions of the cycle checkpoints can allow cancer cells to acquire drug resistance. Etoposide is a well-known inducer of apoptosis, which is widely used in cell biology and in clinical practice. In this work we report that a pulse of 50 microM etoposide (incubation for only 3h) on HeLa cells causes a sequence of events that leads to abnormal mitotic figures that could be followed either by cell death or, more commonly, by interphase restitution and endocycle. The endocycling polyploid cells enter immediately into mitosis and suffer metaphase blockage with multiple spindle poles, which were generally followed by a direct triggering of apoptosis from metaphase (mitotic catastrophe), or by a new process of endocycling, until surviving cells finally became apoptotic (96 h after the treatment).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Cell Death / drug effects
  • Cell Survival / drug effects
  • Etoposide / pharmacology*
  • Etoposide / toxicity
  • Flow Cytometry
  • HeLa Cells
  • Humans
  • Metaphase / drug effects*
  • Microscopy, Electron, Scanning
  • Polyploidy
  • Spindle Apparatus / drug effects


  • Antineoplastic Agents, Phytogenic
  • Etoposide