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.
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.
authors.affiliation: Department of Hematology/Oncology, University of Heidelberg Medical Center, Heidelberg, Germany.
authors.forename: Yaoxian
authors.initials: Y
authors.lastname: Xu
authors.forename: Susanne
authors.initials: S
authors.lastname: Voelter-Mahlknecht
authors.forename: Ulrich
authors.initials: U
authors.lastname: Mahlknecht
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016044:Fusion Proteins, bcr-abl / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000378:metabolism* / Q000473:pathology; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D000077337:Vorinostat; D000099186:Histone Deacetylase 3
chemical_list: D004791:Enzyme Inhibitors; D016044:Fusion Proteins, bcr-abl; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases; D006877:Hydroxamic Acids; D016271:Proto-Oncogene Proteins c-myc; D000077337:Vorinostat; D000099186:Histone Deacetylase 3