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 (Journal article)

Thomas, C. G./ Vezyraki, P. E./ Kalfakakou, V. P./ Evangelou, A. M.

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.
Institution and School/Department of submitter: Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής
Keywords: 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
URI: https://olympias.lib.uoi.gr/jspui/handle/123456789/24561
ISSN: 0021-9541
Link: http://www.ncbi.nlm.nih.gov/pubmed/15887239
http://onlinelibrary.wiley.com/store/10.1002/jcp.20405/asset/20405_ftp.pdf?v=1&t=h0c6japx&s=34c2a57cbace42707143596ce9f283f2a7cfacfd
Appears in Collections:Άρθρα σε επιστημονικά περιοδικά ( Ανοικτά)

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