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Related Experiment Videos

Autoschizis: a novel cell death.

James M Jamison1, Jacques Gilloteaux, Henryk S Taper

  • 1Department of Urology, Summa Health System/Northeastern Ohio Universities College of Medicine, 2209 State Route 44, PO Box 95, Rootstown, OH 44272-0095, USA. jmj@neoucom.edu

Biochemical Pharmacology
|May 30, 2002
PubMed
Summary

Vitamin C (VC) and vitamin K3 (VK3) synergistically kill tumor cells via autoschizis, a novel necrosis. This vitamin combination shows promise in reducing tumor growth and increasing lifespan in mice with minimal toxicity.

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Area of Science:

  • Oncology
  • Biochemistry
  • Cell Biology

Background:

  • Vitamin C (VC) and vitamin K3 (VK3) demonstrate synergistic antitumor activity.
  • Autoschizis is a novel necrosis mechanism involving membrane damage and cytoplasm loss.
  • Tumor cell death induced by VC:VK3 does not stem from ATP depletion.

Purpose of the Study:

  • To elucidate the mechanisms by which VC:VK3 induces tumor-specific cell death via autoschizis.
  • To investigate the role of oxidative stress, calcium signaling, and DNA degradation in VC:VK3-induced autoschizis.

Main Methods:

  • Administration of VC:VK3 at a 100:1 ratio to tumor cells and tumor-bearing mice.
  • Analysis of cell cycle progression, DNA synthesis, H2O2 production, and cellular thiol levels.
  • Measurement of intracellular Ca2+ levels and DNA degradation via electrophoretic analysis.

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  • Assessment of tumor growth rate and lifespan in a mouse model.

    • Main Results:

    • VC:VK3 treatment induced a G1/S block, diminished DNA synthesis, and increased H2O2 production.
    • Catalase prevented VC:VK3 effects, indicating H2O2's crucial role.
    • Intracellular Ca2+ levels increased 8- to 10-fold, activating Ca2+-dependent DNases.
    • Oral VC:VK3 administration in mice reduced tumor growth and increased lifespan without significant toxicity.

    Conclusions:

    • VC:VK3 induces tumor cell death through autoschizis, a process involving oxidative stress, Ca2+ release, and caspase-3-independent DNA degradation.
    • The vitamins reactivate deoxyribonuclease I and II (DNase I, DNase II), leading to DNA fragmentation.
    • VC:VK3 represents a potentially effective and non-toxic therapeutic strategy for cancer treatment.