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The histone deacetylase inhibitor trichostatin A induces cell cycle arrest and rapid upregulation of gadd45β in LS174T human colon cancer cells

Author(s): Kenji Ueda | Tatsuya Abe | Jun Murata | Tomoyuki Taniguchi | Jun Iwashita

Journal: Journal of Biophysical Chemistry
ISSN 2153-036X

Volume: 02;
Issue: 01;
Start page: 43;
Date: 2012;
Original page

Keywords: Histone Deacetylase Inhibitor | Gadd45 Genes | Trichostatin A | LS174T Cells

Histone deacetylase (HDAC) inhibitors are consid- ered as promising therapeutic agents against several malignant diseases because they inhibit cancer cell proliferation. The stress sensor genes of the growth arrest and DNA damage-inducible protein (gadd45) family exhibit disordered expression in several types of malignant diseases and are thus a novel target for cancer therapy. However, there have been only few investigations of whether HDAC inhibitors affect the expression of gadd45 genes. We examined the effects of a HDAC inhibitor, trichostatin A (TSA), on the time-dependent expression of gadd45 genes in the hu- man colon cancer cell line LS174T. Addition of TSA to LS174T cells induced inhibition of cell prolifera-tion by arresting the cell cycle. We found that TSA treatment of LS174T cells induced rapid upregulation of gadd45β mRNA expression within 15 min, reach- ing a peak level at 3 h. Although the time-dependent expression pattern of gadd45β mRNA was similar to that of gadd45β mRNA, the peak level of gadd45β was lower than that of gadd45β. TSA treatment also upregulated the mRNA level of p21Waf1/Cip1, a prolif- eration inhibitor, after 3 h, but downregulated the mRNA levels of cyclin D1, a proliferation inducer, after 3 h, and of c-Myc after 1 h. TSA treatment in- duced a certain level of apoptosis, but the mRNA le- vel of p53, a potent apoptosis inducer, was down-re- gulated after 3 h. These results suggest that the up- regulation of p21Waf1/Cip1 and apoptosis was indepen- dent of p53 and that the early upregulation of gadd45β gene, which precedes the upregulation of p21Waf1/Cip1 and the downregulation of cyclin D1, are important in TSA-treated LS174T cells.

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Tangokurs Rapperswil-Jona

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