Autoschizis: A novel cell death

James M. Jamison, Jacques Gilloteaux, Henryk S. Taper, Pedro Buc Calderon, Jack L Summers

Research output: Contribution to journalReview articlepeer-review


Vitamin C (VC) and vitamin K3 (VK3) administered in a VC:VK3 ratio of 100:1 exhibit synergistic antitumor activity and preferentially kill tumor cells by autoschizis, a novel type of necrosis characterized by exaggerated membrane damage and progressive loss of organelle-free cytoplasm through a series of self-excisions. During this process, the nucleus becomes smaller, cell size decreases one-half to one-third of its original size, and most organelles surround an intact nucleus in a narrow rim of cytoplasm. While the mitochondria are condensed, tumor cell death does not result from ATP depletion. However, vitamin treatment induces a G1/S block, diminishes DNA synthesis, increases H2O2 production, and decreases cellular thiol levels. These effects can be prevented by the addition of catalase to scavenge the H2O2. There is a concurrent 8- to 10-fold increase in intracellular Ca2+ levels. Electrophoretic analysis of DNA reveals degradation due to the caspase-3-independent reactivation of deoxyribonuclease I and II (DNase I, DNase II). Redox cycling of the vitamins is believed to increase oxidative stress until it surpasses the reducing ability of cellular thiols and induces Ca2+ release, which triggers activation of Ca2+-dependent DNase and leads to degradation of DNA. Recent experiments indicate that oral VC:VK3 increases the life-span of tumor-bearing nude mice and significantly reduces the growth rate of solid tumors without any significant toxicity by reactivating DNase I and II and inducing autoschizis. This report discusses the mechanisms of action employed by these vitamins to induce tumor-specific death by autoschizis.

Original languageEnglish
Article number7196
Pages (from-to)1773-1783
Number of pages11
JournalBiochemical Pharmacology
Issue number10
Publication statusPublished - 2002
Externally publishedYes


  • Autoschizis
  • Cell death
  • Menadione
  • Vitamin C
  • Vitamin K


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