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  • Title: The histone deacetylase inhibitor suberoylanilide hydroxamic acid down-regulates expression levels of Bcr-abl, c-Myc and HDAC3 in chronic myeloid leukemia cell lines.
    Author: Xu Y, Voelter-Mahlknecht S, Mahlknecht U.
    Journal: Int J Mol Med; 2005 Jan; 15(1):169-72. PubMed ID: 15583844.
    Abstract:
    In chronic myelocytic leukemia (CML) the activity of the Bcr-Abl tyrosine kinase is known to activate a number of molecular mechanisms, which inhibit apoptosis. In the present study, we show that the histone deacetylase inhibitor SAHA (suberoylanilide hydroxamic acid) markedly decreases protein expression levels of Bcr-Abl and c-Myc in BV-173 cells, while in K562 cells only a minor decrease of Bcr-Abl protein levels is observed while a considerable reduction of c-Myc protein expression may only be achieved at higher concentrations of SAHA. In addition, we found BV-173 cells to be more sensitive to SAHA-induced apoptosis when compared to K562 cells. Even though earlier reports on SAHA considerably focused on its inhibitory effect on HDAC enzymatic activity, we report herein a significant down-regulation of HDAC3 protein expression levels following treatment with SAHA in BV-173 cells, but not in K562 cells. In conclusion, our results imply a molecular mechanism for SAHA-induced apoptosis in BV-173 cells, which involves decreased protein expression levels of Bcr-Abl, c-Myc and HDAC3.
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