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In breast cancer cell lines, SAHA has beenĭemonstrated to suppress the growth of tumor cells in vitroĪt low micromolar concentrations ( 10).
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Human breast tumor cells has been widely investigated. Since breast cancer is the highestĬause of tumor death in women, the antitumoral potency of HDACis on (depsipeptide or FK228), have been approved by the US Food and DrugĪdministration for the treatment of cutaneous T cell lymphoma Inhibit endothelial cell proliferation and angiogenesis byĭown-regulating angiogenesis-related gene expression ( 7). Recent studies have shown that HDAC inhibitors induce cellĬycle arrest, differentiation, and apoptosis in vitro and Peptides without the 2-amino-8-oxo-9,10-epoxy-decanoyl moiety (SAHA and trichostatin A), short-chain fatty acids (sodium butyrateĪnd phenylbutyrate), cyclic tetrapeptide containing aĢ-amino-8-oxo-9,10-epoxy-decanoyl moiety (trapoxin A) and cyclic Five chemical classes of HDACis haveīeen characterized including benzamides (MS-275), hydroxamic acids HDAC inhibitors (HDACis) are a new group ofĪnticancer agents and are currently evaluated in several phase IĪnd phase II clinical trials in patients with hematologic and solid Is well known that hyperacetylation of histones H3 and H4Ĭorrelates with gene activation whereas deacetylation mediatesĬhromatin condensation and gene transcription silencing ( 3). The expression pattern of genes involved in the regulation of cell Histones is often associated with cancer since it causes changes in To our knowledge, this is the first study to indicate that this member of the TNF superfamily, CD137, is modulated by SAHA treatment in breast cancer cells, suggesting that the combination of SAHA with this TNF-related receptor could be a new therapeutic approach for the treatment of tumors.Īltered acetylation and deacetylation of the In particular, we demonstrated that the upregulation of the CD137 receptor/ligand system correlates with a synergistic cytotoxic effect when MDA-MB-231 cells are treated with the combination of SAHA and soluble CD137 receptor. We found that the apoptotic gene pattern induced by SAHA in the MDA-MB-231 cell line involves the upregulation of some molecules belonging to the TNF superfamily. In this study, we investigated the activation of some apoptotic genes which could be responsible for the in vivo antitumor potency of SAHA in a model of human breast cancer. Induction of apoptotic genes is an important pathway of SAHA cytotoxic mechanism of action and it has been largely described that SAHA induces sensitization of cell death receptor-resistant breast cancer cells to apoptosis. HDAC inhibitors (HDACis) represent a class of anticancer agents including suberoylanilide hydroxamic acid (SAHA, Vorinostat), which has shown a strong antitumor effect, both in vitro and in vivo.