Sodium butyrate induces cell senescence in transformed rodent cells resistant to apoptosis
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The capacity of HDAC inhibitor sodium butyrate to induce senescence in cells derived from rat embryonic fibroblasts and transformed by E1A + E1B19 kDa oncogene has been studied. These transformants are resistant to apoptosis in response to γ-irradiation and the deprivation of growth factors. The process of cell senescence was investigated by analyzing cell growth curves, G1/S and G2/M cell cycle arrest and senescent associated β-galactosidase expression. The irreversibility of the antiproliferative activity of sodium butyrate was analyzed by clonogenic assay.
We show that sodium butyrate suppresses proliferation and induces senescence in the E1A + E1B19 kDa transformed cells. Interestingly, NaB induced growth arrest due to the accumulation of cells in the G2/M phase; they are not tetraploid, but mainly binuclear cells. Thus, in the case of NaB induces senescence in E1A + E1B19 kDa transformed fibroblasts, the observed suppression of cell proliferation may be a result of cytokinesis failure, which leads to the formation of binuclear and multinuclear cells incapable of proliferating.
Keywordssodium butyrate histone deacetylase inhibitor cell senescence transformants E1A + E1B19kDa
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