Mitotic catastrophe triggered in human cancer cells by the viral protein apoptin

H L Lanz1, R M E Zimmerman, J Brouwer

  • 1Department of Molecular Genetics, Leiden Institute of Chemistry, Leiden University, Leiden, The Netherlands.

Cell Death & Disease
|February 9, 2013
PubMed

Insights

Apoptin protein from Chicken Anemia Virus (CAV) induces mitotic catastrophe, a cell death process, in cancer cells by causing abnormal spindle formation. This targeted cell death offers a promising therapeutic strategy against tumors.

Area of Science:

  • Oncology
  • Molecular Biology
  • Virology

Background:

  • Mitotic catastrophe is a crucial oncosuppressive mechanism that eliminates cells with mitotic failures, preventing aneuploidy and genetic instability.
  • Inducing mitotic catastrophe in cancer cells is a promising therapeutic strategy.
  • Apoptin, a protein from Chicken Anemia Virus (CAV), selectively induces cell death in human tumor cells.

Purpose of the Study:

  • To investigate the mechanism by which apoptin induces cell death in tumor cells.
  • To determine if apoptin triggers mitotic catastrophe in a p53-independent manner.
  • To evaluate the potential of apoptin as an anti-cancer therapeutic agent.

Main Methods:

  • Osteosarcoma cells were treated with apoptin.
  • Abnormal spindle formation was assessed using microscopy.
  • Mitotic progression was monitored using time-lapse microscopy.
  • Caspase-3 activation was measured in both mitotic and non-mitotic cells.

Main Results:

  • Apoptin induced abnormal spindle formation in approximately 50% of osteosarcoma cells, a tenfold increase compared to controls.
  • Apoptin-expressing cells showed significantly impaired progression through anaphase and telophase.
  • Time-lapse microscopy revealed aberrant mitotic figures and prolonged mitotic duration in apoptin-expressing cells.
  • All dividing cells expressing apoptin underwent cell death during mitosis or interphase.
  • Apoptin also induced caspase-3 activation and apoptosis in non-mitotic cancer cells.

Conclusions:

  • Apoptin efficiently triggers cell death in dividing human tumor cells via mitotic catastrophe.
  • Apoptin's anti-cancer activity extends to non-mitotic cancer cells by inducing apoptosis.
  • Apoptin represents a potential therapeutic agent for cancer treatment, targeting both dividing and non-dividing tumor cells.

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