Document Detail


Endoplasmic reticulum stress plays a pivotal role in cell death mediated by the pan-deacetylase inhibitor panobinostat in human hepatocellular cancer cells.
MedLine Citation:
PMID:  23544167     Owner:  NLM     Status:  PubMed-not-MEDLINE    
Abstract/OtherAbstract:
Panobinostat, a pan-deacetylase inhibitor, represents a novel therapeutic option for cancer diseases. Besides its ability to block histone deacetylases (HDACs) by promoting histone hyperacetylation, panobinostat interferes with several cell death pathways providing a potential efficacy against tumors. We have previously demonstrated that panobinostat has a potent apoptotic activity in vitro and causes a significant growth delay of hepatocellular carcinoma (HCC) tumor xenografts in nude mice models. Here, we show that treatment with panobinostat is able to induce noncanonical apoptotic cell death in HepG2 and in Hep3B cells, involving the endoplasmic reticulum (ER) stress by up-regulation of the molecular chaperone binding immunoglobulin protein/glucose-regulated protein 78, activation of eukaryotic initiation factor 2α-activating transcription factor 4 (tax-responsive enhancer element B67) and inositol requiring 1α-X-box binding protein 1 factors, strong increase and nuclear translocation of the transcription factor C/EBP homologous protein/growth arrest and DNA damage-inducible gene 153, and involvement of c-Jun N-terminal kinase. These signaling cascades culminate into the activation of the ER-located caspase-4/12 and of executioner caspases, which finally lead to cell demise. Our results clearly show that panobinostat induces an alternative ER stress-mediated cell death pathway in HCC cells, independent of the p53 status.
Authors:
Roberta Montalbano; Petra Waldegger; Karl Quint; Samir Jabari; Daniel Neureiter; Romana Illig; Matthias Ocker; Pietro Di Fazio
Related Documents :
23769837 - Cells of renin lineage are progenitors of podocytes and parietal epithelial cells in ex...
23455057 - Microwave-assisted synthesis of arene ruthenium(ii) complexes that induce s-phase arres...
23139287 - Genetic cre-loxp assessment of epicardial cell fate using wt1-driven cre alleles.
25138357 - Yeast studies reveal moonlighting functions of the ancient actin cytoskeleton.
20964597 - Receptor-mediated gene delivery by folate-poly(ethylene glycol)-grafted-trimethyl chito...
23867747 - Histone signature of metanephric mesenchyme cell lines.
Publication Detail:
Type:  Journal Article     Date:  2013-04-01
Journal Detail:
Title:  Translational oncology     Volume:  6     ISSN:  1936-5233     ISO Abbreviation:  Transl Oncol     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-04-01     Completed Date:  2013-04-02     Revised Date:  2013-04-03    
Medline Journal Info:
Nlm Unique ID:  101472619     Medline TA:  Transl Oncol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  143-57     Citation Subset:  -    
Affiliation:
Institute for Surgical Research, Philipps University of Marburg, Marburg, Germany.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  DW-MRI as a Predictive Biomarker of Radiosensitization of GBM through Targeted Inhibition of Checkpo...
Next Document:  Imatinib and Dasatinib Inhibit Hemangiosarcoma and Implicate PDGFR-? and Src in Tumor Growth.