Autoschizis: a novel cell death.

Title

Autoschizis: a novel cell death.

Creator

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

Publisher

Biochemical pharmacology

Date

2002
2002-05

Description

Vitamin C (VC) and vitamin K(3) (VK(3)) administered in a VC:VK(3) 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 G(1)/S block, diminishes DNA synthesis, increases H(2)O(2) production, and decreases cellular thiol levels. These effects can be prevented by the addition of catalase to scavenge the H(2)O(2). There is a concurrent 8- to 10-fold increase in intracellular Ca(2+) 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 Ca(2+) release, which triggers activation of Ca(2+)-dependent DNase and leads to degradation of DNA. Recent experiments indicate that oral VC:VK(3) 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.

Subject

Animals; Antioxidants/chemistry/*pharmacology/therapeutic use; Ascorbic Acid/chemistry/*pharmacology/therapeutic use; Cell Death/*physiology; Humans; Necrosis; Neoplasms/drug therapy/metabolism/*pathology; Oxidative Stress/*drug effects; Vitamin K/chemistry/*pharmacology/therapeutic use

Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

1773–1783

Issue

10

Volume

63

Citation

Jamison James M; Gilloteaux Jacques; Taper Henryk S; Calderon Pedro Buc; Summers Jack L, “Autoschizis: a novel cell death.,” NEOMED Bibliography Database, accessed December 6, 2021, https://neomed.omeka.net/items/show/3831.

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