| Proteasome inhibition potentiates the cytotoxic effects of hyperthermia in HT-29 colon cancer cells through inhibition of heat shock protein 27. | |
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MedLine Citation:
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PMID: 18337621 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Fei Chen; Reza Rezavi; Cha-Chi Wang; Lawrence E Harrison |
Publication Detail:
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Type: Journal Article Date: 2008-03-13 |
Journal Detail:
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Title: Oncology Volume: 73 ISSN: 1423-0232 ISO Abbreviation: Oncology Publication Date: 2007 |
Date Detail:
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Created Date: 2008-03-31 Completed Date: 2008-04-14 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0135054 Medline TA: Oncology Country: Switzerland |
Other Details:
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Languages: eng Pagination: 98-103 Citation Subset: IM |
Copyright Information:
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(c) 2008 S. Karger AG, Basel |
Affiliation:
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Division of Surgical Oncology, UMDNJ - New Jersey Medical School, Newark, NJ 07103, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antineoplastic Agents
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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 Humans Hyperthermia, Induced* Leupeptins / pharmacology Nitriles / pharmacology Protease Inhibitors / pharmacology Proteasome Endopeptidase Complex / antagonists & inhibitors* RNA, Small Interfering / metabolism |
| Chemical | |
Reg. No./Substance:
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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 3.4.25.1/Proteasome Endopeptidase Complex |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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