SODIUM BUTYRATE INDUCED CELL SENESCENCE IN RODENT TRANSFORMED CELLS RESISTANT TO APOPTOSIS
Z. V. Chitikova,1, 2 N. D. Aksenov,1 V. A. Pospelov,1, 2 T. V. Pospelova 1, 2
1 Institute of Cytology Russian Academy of Sciences, Saint-Petersburg, and 2 Saint-Petersburg State University;
e-mail: zhanna_shi@mail.ru
The capacity of HDAC inhibitor sodium butyrate to induce senescence in cells derived from rat embryonic fibroblasts transformed by E1A+E1B19kDa oncogenes has been studied.
These transformants are resistant to apoptosis in response to γ -irradiation and growth factor deprivation. The process of cell senescence was investigated by the analysis of cell
growth curves, G1/S and G2/M cell cycle arrest, and senescent associated β-galactosidase expression. The irreversibility of sodium butyrate antiproliferative
activity was analyzed by clonogenic assay.
We show that sodium butyrate suppresses proliferation and induces senescence in the E1A+E1B19kDa transformed cells. Interestingly, NaB induces growth arrest due to accumulation
of cells in G2/M phase, these cells are not tetraploid but mainly binuclear. Thus, in case of NaB induced senescence in E1A+E1B19kDa transformed fibroblasts, the observed
suppression of cell proliferation may be the result of cytokinesis failure leading to formation of binuclear and multinuclear cells incapable to proliferate.
Key words: sodium butyrate, histone deacetylase inhibitor, cell senescence, transformants E1A+E1B19kDa
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