| Abstrakt: |
Inhibitors of histone-deacetylase activity are widely used to block cancer cell proliferation in clinical trials in vivo and in experiments involving tumor cells in vitro. In addition to suppressing tumor-cell proliferation, these inhibitors can induce either cell senescence or apoptotic cell death and autophagy. Histone deacetylase 6 (HDAC6, class II) differs from other HDACs (class I) in its predominantly cytoplasmic localization and low histone deacetylase activity. Moreover, HDAC6 deacetylates a number of non-histone proteins, including α-tubulin, a microtubule component, thereby affecting their stability. Overexpression of HDAC6 has been found in various tumor-cell lines and induced tumors in mice. Available evidence suggests that HDAC6 is involved in the control of the autophagy process, as α-tubulin acetylation is required for autophagosome fusion with lysosomes. In the present work, we compared effects of the HDAC inhibitor sodium butyrate and tubacin, a specific inhibitor of HDAC6, on E1A+Ras-transformed mouse fibroblasts (mERas line). Sodium butyrate inhibits the activity of HDAC I (but not HDAC6). It turned out that tubacin causes the same effects as sodium butyrate in terms of inhibition of cell growth, induction of a cell-cycle block at the G1/S phase boundary, and cellular senescence. Since tubacin induces α-tubulin acetylation, it can be assumed that a certain level of α-tubulin acetylation is required for the proliferation, senescence, and migration of mERas cells. [ABSTRACT FROM AUTHOR] |
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