scholarly journals Suberoylanilide Hydroxamic Acid (Vorinostat) Up-regulates Progranulin Transcription

2011 ◽  
Vol 286 (18) ◽  
pp. 16101-16108 ◽  
Author(s):  
Basar Cenik ◽  
Chantelle F. Sephton ◽  
Colleen M. Dewey ◽  
Xunde Xian ◽  
Shuguang Wei ◽  
...  
Keyword(s):  
Frontotemporal Dementia ◽  
Hydroxamic Acid ◽  
First Generation ◽  
Cultured Cells ◽  
Therapeutic Potential ◽  
Human Subjects ◽  
Suberoylanilide Hydroxamic Acid ◽  
Chemical Library ◽  
Protein Levels ◽  
Deacetylase Inhibitor

Progranulin (GRN) haploinsufficiency is a frequent cause of familial frontotemporal dementia, a currently untreatable progressive neurodegenerative disease. By chemical library screening, we identified suberoylanilide hydroxamic acid (SAHA), a Food and Drug Administration-approved histone deacetylase inhibitor, as an enhancer of GRN expression. SAHA dose-dependently increased GRN mRNA and protein levels in cultured cells and restored near-normal GRN expression in haploinsufficient cells from human subjects. Although elevation of secreted progranulin levels through a post-transcriptional mechanism has recently been reported, this is, to the best of our knowledge, the first report of a small molecule enhancer of progranulin transcription. SAHA has demonstrated therapeutic potential in other neurodegenerative diseases and thus holds promise as a first generation drug for the prevention and treatment of frontotemporal dementia.

Cotreatment with the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) enhances imatinib-induced apoptosis of Bcr-Abl–positive human acute leukemia cells

Blood ◽  
2003 ◽  
Vol 101 (8) ◽  
pp. 3236-3239 ◽  
Author(s):  
Ramadevi Nimmanapalli ◽  
Lianne Fuino ◽  
Corinne Stobaugh ◽  
Victoria Richon ◽  
Kapil Bhalla
Keyword(s):  
Histone Deacetylases ◽  
Hydroxamic Acid ◽  
Blast Crisis ◽  
Cell Types ◽  
Suberoylanilide Hydroxamic Acid ◽  
Cytotoxic Effects ◽  
Protein Levels ◽  
Myelocytic Leukemia ◽  
Deacetylase Inhibitor ◽  
Induced Apoptosis

Abstract Here we demonstrate that treatment with SAHA (suberoylanilide hydroxamic acid), a known inhibitor of histone deacetylases (HDACs), alone induced p21 and/or p27 expressions but decreased the mRNA and protein levels of Bcr-Abl, which was associated with apoptosis of Bcr-Abl–expressing K562 and LAMA-84 cells. Cotreatment with SAHA and imatinib (Gleevec) caused more down-regulation of the levels and auto-tyrosine phosphorylation of Bcr-Abl and apoptosis of these cell types, as compared with treatment with either agent alone (P < .05). This finding was also associated with a greater decline in the levels of phospho-AKT and Bcl-xL. Significantly, treatment with SAHA also down-regulated Bcr-Abl levels and induced apoptosis of CD34+ leukemia blast progenitor cells derived from patients who had developed progressive blast crisis (BC) of chronic myelocytic leukemia (CML) while receiving therapy with imatinib. Taken together, these findings indicate that cotreatment with SAHA enhances the cytotoxic effects of imatinib and may have activity against imatinib-refractory CML-BC.

scholarly journals Modified Cap Group Suberoylanilide Hydroxamic Acid Histone Deacetylase Inhibitor Derivatives Reveal Improved Selective Antileukemic Activity

2010 ◽  
Vol 53 (8) ◽  
pp. 3038-3047 ◽  
Author(s):  
Chanaz Salmi-Smail ◽  
Aurélie Fabre ◽  
Franck Dequiedt ◽  
Audrey Restouin ◽  
Rémy Castellano ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitor ◽  
Hydroxamic Acid ◽  
Suberoylanilide Hydroxamic Acid ◽  
Antileukemic Activity ◽  
Deacetylase Inhibitor
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