The Therapeutic Potential of AN-7, a Novel Histone Deacetylase Inhibitor, for Treatment of Mycosis Fungoides/Sezary Syndrome Alone or with Doxorubicin
Autor: | Ido Lubin, Emmilia Hodak, Batia Gorovitz, Lilach Moyal, Nataly Tarasenko, Nataly Feldbaum, Ada Rephaeli, Iris Amitay-Laish, Michal Weitman, Neta Goldfeiz, Abraham Nudelman, Leah Maron, Shiran Yehezkel |
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Jazyk: | angličtina |
Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
medicine.drug_class Cell Survival lcsh:Medicine Down-Regulation Apoptosis Pharmacology Biology Hydroxamic Acids Histone Deacetylases Romidepsin Cell Line Phosphates Histones 03 medical and health sciences 0302 clinical medicine Mycosis Fungoides Organophosphorus Compounds medicine Humans Sezary Syndrome Doxorubicin Viability assay Lymphocytes lcsh:Science Vorinostat Mycosis fungoides Multidisciplinary Histone deacetylase inhibitor lcsh:R Acetylation medicine.disease Organophosphates Histone Deacetylase Inhibitors Butyrates 030104 developmental biology Cell culture 030220 oncology & carcinogenesis lcsh:Q Drug Therapy Combination medicine.drug Research Article |
Zdroj: | PLoS ONE PLoS ONE, Vol 11, Iss 1, p e0146115 (2016) |
ISSN: | 1932-6203 |
Popis: | The 2 histone deacetylase inhibitors (HDACIs) approved for the treatment of cutaneous T-cell lymphoma (CTCL) including mycosis fungoides/sezary syndrome (MF/SS), suberoylanilide hydroxamic acid (SAHA) and romidepsin, are associated with low rates of overall response and high rates of adverse effects. Data regarding combination treatments with HDACIs is sparse. Butyroyloxymethyl diethylphosphate (AN-7) is a novel HDACI, which was found to have selective anticancer activity in several cell lines and animal models. The aim of this study was to compare the anticancer effects of AN-7 and SAHA, either alone or combined with doxorubicin, on MF/SS cell lines and peripheral blood lymphocytes (PBL) from patients with Sezary syndrome (SPBL). MyLa cells, Hut78 cells, SPBL, and PBL from healthy normal individuals (NPBL) were exposed to the test drugs, and the findings were analyzed by a viability assay, an apoptosis assay, and Western blot. AN-7 was more selectively toxic to MyLa cells, Hut78 cells, and SPBL (relative to NPBL) than SAHA and also acted more rapidly. Both drugs induced apoptosis in MF/SS cell lines, SAHA had a greater effect on MyLa cell line, while AN-7 induced greater apoptosis in SPBL; both caused an accumulation of acetylated histone H3, but AN-7 was associated with earlier kinetics; and both caused a downregulation of the HDAC1 protein in MF/SS cell lines. AN-7 acted synergistically with doxorubicin in both MF/SS cell lines and SPBL, and antagonistically with doxorubicin in NPBL. By contrast, SAHA acted antagonistically with doxorubicin on MF/SS cell lines, SPBL, and NPBL, leaving |
Databáze: | OpenAIRE |
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