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Vitamin C transiently arrests cancer cell cycle progression in S phase and G 2 /M boundary by modulating the kinetics of activation and the subcellular localization of Cdc25C phosphatase
Author(s) -
Thomas Christopher G.,
Vezyraki Patra E.,
Kalfakakou Vicky P.,
Evangelou Angelos M.
Publication year - 2005
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.20405
Subject(s) - mitosis , cyclin dependent kinase 1 , cyclin b1 , cell cycle , microbiology and biotechnology , ascorbic acid , hela , chemistry , cyclin , biochemistry , biology , cell , food science
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 G 2 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. © 2005 Wiley‐Liss, Inc.