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Inhibition of G 1 cell cycle arrest in human gingival fibroblasts exposed to phenytoin
Author(s) -
Takeuchi Reiri,
Matsumoto Hiroko,
Akimoto Yoshiaki,
Fujii Akira
Publication year - 2014
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.2012.01065.x
Subject(s) - cell cycle , cell growth , cell cycle checkpoint , fibroblast , chemistry , phenytoin , cell , microbiology and biotechnology , endocrinology , medicine , biology , biochemistry , in vitro , neuroscience , epilepsy
Gingival overgrowth is caused in response to the antiepileptic drug phenytoin ( PHT ). PHT ‐induced gingival overgrowth is characterized by the proliferation of fibroblasts and increased collagen formation in gingiva. Fibroblast proliferation is regulated through the cell cycle. Thus, in the present study, we examined the effects of PHT on the cell cycle, the expression of cell cycle control proteins and the proliferation in human gingival fibroblasts ( hGF s). Cells were stimulated in serum‐free DMEM with or without 0.25 μ m PHT . Subsequently, the cell cycle phase distribution and the protein expression after 24 h and the cell proliferation after 24, 48 and 72 h were evaluated. PHT significantly inhibited synchronization at the G 0 / G 1 phase of the cell cycle in hGF s through serum starvation. Stimulation with PHT for 48 and 72 h significantly induced a proliferative response in hGF s. PHT decreased the expression of the C dk‐inhibitory proteins p21 and p27 and increased the levels of the S phase‐promoting proteins phospho‐Thr160‐ C dk2 and phospho‐ S er807/811‐ R b in serum‐free DMEM . The inhibition of G 1 cell cycle arrest in hGF s may result from an increase in phosphorylated C dk2 and R b proteins and decreased levels of p21 and p27 proteins by PHT . The gingival overgrowth may be caused by the failure of the G1 cell cycle arrest in GFs exposed to PHT .