Document Detail

Proteasome inhibition potentiates the cytotoxic effects of hyperthermia in HT-29 colon cancer cells through inhibition of heat shock protein 27.
MedLine Citation:
PMID:  18337621     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: The purpose of this study was to investigate whether proteasome inhibition acts as a thermal sensitizing agent to induce tumor cell death in a colon cancer cell line. METHODS: HT-29 colon cancer cells were exposed to hyperthermia (43 degrees C) in the presence of proteasome inhibition for 1 h. Viable cell mass and apoptosis were measured by MTT and annexin V staining, respectively. Protein levels were determined by Western blot analysis. RESULTS: A significant synergistic effect on cell viability with proteasome inhibition was noted under hyperthermic conditions compared to hyperthermia alone (p < 0.05). Increases in phosphorylated ERK and decreases in HSP27 levels were observed in the cells exposed to proteasome inhibition at 43 degrees C. Pretreatment with an inhibitor of ERK yielded an additional increase in apoptosis when used in combination with proteasome inhibition and hyperthermia. Decreased expression of HSP27 by siRNA also resulted in increased thermally induced apoptotic cell death. CONCLUSIONS: Thermal sensitization through proteasome inhibition may represent a novel approach to increase the efficacy of hyperthermia as an anticancer modality.
Fei Chen; Reza Rezavi; Cha-Chi Wang; Lawrence E Harrison
Publication Detail:
Type:  Journal Article     Date:  2008-03-13
Journal Detail:
Title:  Oncology     Volume:  73     ISSN:  1423-0232     ISO Abbreviation:  Oncology     Publication Date:  2007  
Date Detail:
Created Date:  2008-03-31     Completed Date:  2008-04-14     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0135054     Medline TA:  Oncology     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  98-103     Citation Subset:  IM    
Copyright Information:
(c) 2008 S. Karger AG, Basel
Division of Surgical Oncology, UMDNJ - New Jersey Medical School, Newark, NJ 07103, USA.
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MeSH Terms
Antineoplastic Agents / pharmacology*
Apoptosis* / drug effects
Blotting, Western
Butadienes / pharmacology
Cell Proliferation / drug effects
Cell Survival / drug effects
Colonic Neoplasms / drug therapy,  enzymology,  metabolism*,  therapy*
Cysteine Proteinase Inhibitors / pharmacology
Dose-Response Relationship, Drug
Drug Synergism
Electrophoresis, Polyacrylamide Gel
Enzyme Inhibitors / pharmacology*
HT29 Cells
Heat-Shock Proteins / antagonists & inhibitors*,  genetics
Hyperthermia, Induced*
Leupeptins / pharmacology
Nitriles / pharmacology
Protease Inhibitors / pharmacology
Proteasome Endopeptidase Complex / antagonists & inhibitors*
RNA, Small Interfering / metabolism
Reg. No./Substance:
0/Antineoplastic Agents; 0/Butadienes; 0/Cysteine Proteinase Inhibitors; 0/Enzyme Inhibitors; 0/Heat-Shock Proteins; 0/Leupeptins; 0/Nitriles; 0/Protease Inhibitors; 0/RNA, Small Interfering; 0/U 0126; 0/carbobenzoxy-leucyl-leucyl-norvalinal; 133407-82-6/benzyloxycarbonylleucyl-leucyl-leucine aldehyde; EC Endopeptidase Complex

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

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