The histone deacetylase inhibitor suberoylanilide hydroxamic acid down-regulates expression levels of Bcr-abl, c-Myc and HDAC3 in chronic myeloid leukemia cell lines |
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Authors: | Xu Yaoxian Voelter-Mahlknecht Susanne Mahlknecht Ulrich |
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Affiliation: | Department of Hematology/Oncology, University of Heidelberg Medical Center, Heidelberg, Germany. |
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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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