Document Detail


Vitamin C transiently arrests cancer cell cycle progression in S phase and G2/M boundary by modulating the kinetics of activation and the subcellular localization of Cdc25C phosphatase.
MedLine Citation:
PMID:  15887239     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Regulation of cell cycle progression involves redox (oxidation-reduction)-dependent modification of proteins including the mitosis-inducing phosphatase Cdc25C. The role of vitamin C (ascorbic acid, ASC), a known modulator of the cellular redox status, in regulating mitotic entry was investigated in this study. We demonstrated that vitamin C inhibits DNA synthesis in HeLa cells and, mainly the form of dehydroascorbic acid (DHA), delays the entry of p53-deficient synchronized HeLa and T98G cancer cells into mitosis. High concentrations of Vitamin C caused transient S and G2 arrest in both cell lines by delaying the activation of the M-phase promoting factor (MPF), Cdc2/cyclin-B complex. Although vitamin C did not inhibit the accumulation of cyclin-B1, it may have increased the level of Cdc2 inhibitory phosphorylation. This was achieved by transiently maintaining Cdc25C, the activator of Cdc2, both in low levels and in a phosphorylated on Ser216 inactive form that binds to 14-3-3 proteins contributing thus to the nuclear exclusion of Cdc25C. As expected, vitamin C prevented the nuclear accumulation of Cdc25C in both cell lines. In conclusion, it seems that vitamin C induces transient cell cycle arrest, at least in part, by delaying the accumulation and the activation of Cdc25C.
Authors:
Christopher G Thomas; Patra E Vezyraki; Vicky P Kalfakakou; Angelos M Evangelou
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of cellular physiology     Volume:  205     ISSN:  0021-9541     ISO Abbreviation:  J. Cell. Physiol.     Publication Date:  2005 Nov 
Date Detail:
Created Date:  2005-09-05     Completed Date:  2005-12-22     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0050222     Medline TA:  J Cell Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  310-8     Citation Subset:  IM    
Copyright Information:
Copyright 2005 Wiley-Liss, Inc.
Affiliation:
Laboratory of Physiology, Unit of Cellular and Molecular Physiology, Faculty of Medicine, University of Ioannina, Ioannina, Greece.
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MeSH Terms
Descriptor/Qualifier:
Antioxidants / pharmacology
Ascorbic Acid / pharmacology*
Cell Cycle / drug effects*
Cell Cycle Proteins / metabolism*
Cell Line, Tumor
DNA / antagonists & inhibitors,  biosynthesis
Enzyme Activation / drug effects
G2 Phase / drug effects*
Hela Cells
Humans
Kinetics
Mitosis / drug effects*
Models, Biological
S Phase / drug effects*
cdc25 Phosphatases / metabolism*
Chemical
Reg. No./Substance:
0/Antioxidants; 0/Cell Cycle Proteins; 50-81-7/Ascorbic Acid; 9007-49-2/DNA; EC 3.1.3.48/CDC25C protein, human; EC 3.1.3.48/cdc25 Phosphatases

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