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Synergistic activity of histone deacetylase and proteasome inhibition against pancreatic and hepatocellular cancer cell lines.
MedLine Citation:
PMID:  21508352     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
MATERIALS AND METHODS: Antiproliferative effects were assessed using a sulforhodamine B assay. Synergy was evaluated using the Chou and Talalay method. Apoptosis was measured by caspase-3/-7 activity and PARP cleavage. Downstream effector proteins were detected via immunoblotting. Quantitative nuclear magnetic resonance (NMR)-based metabolomics analysis was performed.
RESULTS: There were single-agent antiproliferative effects against PC and HCC cell lines; the combination of bel and bor (bel+bor) had a synergistic effect. There was up to a 45-fold induction of apoptosis over the control. Post-treatment cell death was associated with p21 up-regulation, more pronounced with treatment with bel+bor. Treatment with bel+bor enhanced hyperacetylation of histone H3 over single-agent bel. A metabolic signature was established for treatments with bor and bel+bor.
CONCLUSION: The combination of bel+bor displayed significant antiproliferative activity against PC and HCC cell lines, with exhibiting synergistic antiproliferative and proapoptotic patterns even at suboptimal single-agent doses.
Authors:
J L Spratlin; T M Pitts; G N Kulikowski; M P Morelli; J J Tentler; N J Serkova; S G Eckhardt
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Anticancer research     Volume:  31     ISSN:  1791-7530     ISO Abbreviation:  Anticancer Res.     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-04-21     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8102988     Medline TA:  Anticancer Res     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  1093-103     Citation Subset:  IM    
Affiliation:
MD FRCPC, Medical Oncology, Cross Cancer Institute, University of Alberta, 11560 University Avenue, Edmonton, Alberta, Canada, T6G. jennifer.spratlin@albertahealthservices.ca.
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