INDUCTION OF PREMATURE SENESCENCE PROGRAM BY AN INHIBITOR OF HISTONE DEACETYLASE SODIUM BUTYRATE IN NORMAL
AND TRANSFORMED RAT FIBROBLASTS
Yu. G. Zubova, T. V. Bykova, S. G. Zubova, M. V. Abramova, N. D. Aksenov,
V. A. Pospelov, T. V. Pospelova
Institute of Cytology RAS, St. Petersburg, Russia;
e-mail: jul_zubova@mail333.com
We investigated a possibility to induce the premature cell senescence in rat embryo fibroblasts and E1A +
cHa-ras transformants. We found that after the treatment with sodium butyrate, an inhibitor of histone deacetylases,
both normal and transformed cells completely stopped to proliferate and accumulated at G1/S and G2/M phases
of the cell cycle. The cloning efficiency data show that the cell cycle arrest induced by sodium butyrate is irreversible and
correlates with the accumulation of active phosphorylated form of stress kinase p38, and with the expression of marker of
senescence - β-galactosidase activity (SA β-Gal). The program resembling the premature senescence after sodium butyrate
treatment is supposed to develop both in normal and transformed cells. The irreversible block of proliferation in E1A +
cHa-ras transformants may be regarded as an example of activation of anticancer program like that of premature senescence in
the tumor rodent cells.
Key words: transformation, senescence, cell cycle, histone deacetylase inhibitor
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