Back to Search
Start Over
Autoschizis: a novel cell death
- Source :
-
Biochemical Pharmacology . May2002, Vol. 63 Issue 10, p1773. 11p. - Publication Year :
- 2002
-
Abstract
- 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. [Copyright &y& Elsevier]
- Subjects :
- *VITAMIN C
*VITAMIN K
*CELL death
Subjects
Details
- Language :
- English
- ISSN :
- 00062952
- Volume :
- 63
- Issue :
- 10
- Database :
- Academic Search Index
- Journal :
- Biochemical Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 7814521
- Full Text :
- https://doi.org/10.1016/S0006-2952(02)00904-8